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Nagase T, Yasuhara T, Kin K, Sasada S, Kawauchi S, Yabuno S, Sugahara C, Hirata Y, Miyake H, Sasaki T, Kawai K, Tanimoto S, Saijo T, Tanaka S. Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke. Exp Neurol 2025; 386:115145. [PMID: 39805465 DOI: 10.1016/j.expneurol.2025.115145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 12/26/2024] [Accepted: 01/08/2025] [Indexed: 01/16/2025]
Abstract
Ischemic stroke results in significant long-term disability and mortality worldwide. Although existing therapies, such as recombinant tissue plasminogen activator and mechanical thrombectomy, have shown promise, their application is limited by stringent conditions. Mesenchymal stem cell (MSC) transplantation, especially using SB623 cells (modified human bone marrow-derived MSCs), has emerged as a promising alternative, promoting neurogenesis and recovery. This study evaluated the effects of voluntary and forced exercise, alone and in combination with SB623 cell transplantation, on neurological and psychological outcomes in a rat model of ischemic stroke. Male Wistar rats that had undergone middle cerebral artery occlusion (MCAO) were divided into six groups: control, voluntary exercise (V-Ex), forced exercise (F-Ex), SB623 transplantation, SB623 + V-Ex, and SB623 + F-Ex. Voluntary exercise was facilitated using running wheels, while forced exercise was conducted on treadmills. Neurological recovery was assessed using the modified neurological severity score (mNSS). Psychological symptoms were evaluated through the open field test (OFT) and forced swim test (FST), and neurogenesis was assessed via BrdU labeling. Both exercise groups exhibited significant changes in body weight post-MCAO. Both exercises enhanced the treatment effect of SB623 transplantation. The forced exercise showed a stronger treatment effect on ischemic stroke than voluntary exercise alone, and the sole voluntary exercise improved depression-like behavior. The SB623 + F-Ex group demonstrated the greatest improvements in motor function, infarct area reduction, and neurogenesis. The SB623 + V-Ex group was most effective in alleviating depression-like behavior. Future research should optimize these exercise protocols and elucidate the underlying mechanisms to develop tailored rehabilitation strategies for stroke patients.
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Affiliation(s)
- Takayuki Nagase
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
| | - Takao Yasuhara
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Kyohei Kin
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Susumu Sasada
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Satoshi Kawauchi
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Satoru Yabuno
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Chiaki Sugahara
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Yuichi Hirata
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
| | - Hayato Miyake
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Tatsuya Sasaki
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
| | - Koji Kawai
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Shun Tanimoto
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
| | - Tomoya Saijo
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
| | - Shota Tanaka
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
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Skelton H, Grogan D, Kotlure A, Berglund K, Gutekunst CA, Gross R. Adaptive wheel exercise for mouse models of Parkinson's Disease. J Neurosci Methods 2025; 414:110314. [PMID: 39532188 DOI: 10.1016/j.jneumeth.2024.110314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 10/06/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Physical exercise has been extensively studied for its therapeutic properties in neurological disease, particularly Parkinson's Disease (PD). However, the established techniques for exercise in mice are not well suited to motor-deficient disease-model animals, rely on spontaneous activity or force exercise with aversive stimuli, and do not facilitate active measurement of neurophysiology with tethered assays. Motorized wheel exercise may overcome these limitations, but has not been shown to reliably induce running in mice. NEW METHOD We developed an apparatus and technique for inducing exercise in mice without aversive stimuli, using a motorized wheel that dynamically responds to subject performance. RESULTS A commercially available motorized wheel system did not satisfactorily provide for exercise, as mice tended to avoid running at higher speeds. Our adaptive wheel exercise platform allowed for effective exercise induction in the 6-hydroxydopamine mouse model of PD, including with precise behavioral measurements and synchronized single-unit electrophysiology. COMPARISON WITH EXISTING METHODS Our approach provides a superior physical platform and programming strategy compared to previously described techniques for motorized wheel exercise. Unlike voluntary exercise, this allows for controlled experimental induction of running, without the use of aversive stimuli that is typical of treadmill-based techniques. CONCLUSIONS Adaptive wheel exercise should allow for physical exercise to be better studied as a dynamic, physiological intervention in parkinsonian mice, as well as other neurological disease models.
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Affiliation(s)
- Henry Skelton
- Department of Neurosurgery, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA 30322, United States; Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr NW, Atlanta, GA 30332, United States.
| | - Dayton Grogan
- Department of Neurosurgery, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA 30322, United States.
| | - Amrutha Kotlure
- Department of Neurosurgery, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA 30322, United States.
| | - Ken Berglund
- Department of Neurosurgery, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA 30322, United States.
| | - Claire-Anne Gutekunst
- Department of Neurosurgery, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA 30322, United States.
| | - Robert Gross
- Department of Neurosurgery, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA 30322, United States; Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Dr NW, Atlanta, GA 30332, United States.
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Brishti A, Johnson SJ, Palmer DG, Raihan MO, Yan L, Casperson SL. Effects of defined voluntary running distances coupled with high-fat diet consumption on the skeletal muscle transcriptome of male mice. Physiol Rep 2025; 13:e70170. [PMID: 39821584 PMCID: PMC11738645 DOI: 10.14814/phy2.70170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 12/16/2024] [Accepted: 12/16/2024] [Indexed: 01/19/2025] Open
Abstract
Exercise counters many adverse health effects of consuming a high-fat diet (HFD). However, complex molecular changes that occur in skeletal muscle in response to exercising while consuming a HFD are not yet known. We investigated the interplay between diverse exercise regimes and HFD consumption on the adaptation of skeletal muscle transcriptome. C57BL/6 male mice were randomized into five groups-one sedentary control group and four exercise groups. The exercise groups consisted of an unrestricted running group (8.3 km/day) and three groups that were restricted to 75%, 50%, or 25% of unrestricted running (6.3, 4.2, and 2.1 km/day, respectively). Total RNA was extracted from frozen gastrocnemius muscle for transcriptome analyses. DEG counts were 1347, 1823, 1103, and 1107 and there were 107, 169, 67, and 89 unique genes present in the HFD-25%, HFD-50%, HFD-75%, and HFD-U, respectively. Comparing exercise groups, we found that exercising at 50% resulted in the most differentially expressed transcripts with the MAPK and PPAR signaling pathways enriched in down- and up-regulated genes, respectively. These results demonstrate that running distance impacts the adaptation of the skeletal muscle transcriptome to exercise and suggest that middle-distance running may provide the greatest protection against high-fat diet-induced stress coupled with exercise.
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Affiliation(s)
- Afrina Brishti
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
| | - Sarah J. Johnson
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
- Present address:
Department of Biomedical Sciences, School of Medicine and Health SciencesUniversity of North DakotaGrand ForksNorth DakotaUSA
| | - Daniel G. Palmer
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
| | - Md Obayed Raihan
- Department of Pharmaceutical Sciences, College of Health Sciences and PharmacyChicago State UniversityChicagoIllinoisUSA
| | - Lin Yan
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
| | - Shanon L. Casperson
- United States Department of Agriculture, Agricultural Research ServiceGrand Forks Human Nutrition Research CenterGrand ForksNorth DakotaUSA
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Wilson KF, Fox AE. Exercise recovers weight gain, but not increased impulsive choice, caused by a high-fat diet. Appetite 2024; 203:107668. [PMID: 39245366 DOI: 10.1016/j.appet.2024.107668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 09/03/2024] [Accepted: 09/05/2024] [Indexed: 09/10/2024]
Abstract
A high-fat diet has negative effects on physical, neurological, and behavioral outcomes. One consistent finding is that a diet high in fat increases impulsive choice behavior-behavior that is linked to a wide range of other negative health behaviors. While the mechanism for this increase in impulsive choice is not well understood, exercise, with its well-known and many benefits, may serve as an effective and accessible way to combat increased impulsive choice associated with a high-fat diet. The goal of this work was to test this possibility. Rats were divided into four groups in a two-by-two factorial design: exercise and control diet, sedentary and control diet, exercise and high-fat diet, sedentary and high-fat diet. Rats in the exercise groups engaged in 30-min of forced, moderate intensity wheel-running exercise five days per week. Rats in the high-fat diet groups ate a diet high in fat. Impulsive choice was measured using a delay discounting task. Exercise prevented weight gain associated with the high-fat diet. Exercise also preserved relative motivation for food reinforcement. However, exercise did not prevent increases in impulsive choice observed for rats that consumed a high-fat diet relative to the rats that consumed the control diet. This work rules out several possible mechanisms by which a high-fat diet may increase impulsive choice behavior. It makes clear that exercise alone may not stave off increases in impulsive choice caused by a high-fat diet. Future work is necessary to uncover the underlying mechanism for this effect and discover interventions, perhaps ones that combine both physically and cognitively demanding activities, to improve health and behavior as it relates to decision making processes.
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Affiliation(s)
- Keenan F Wilson
- Department of Psychology, St. Lawrence University, United States
| | - Adam E Fox
- Department of Psychology, St. Lawrence University, United States.
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Szilágyi A, Takács B, Szekeres R, Tarjányi V, Nagy D, Priksz D, Bombicz M, Kiss R, Szabó AM, Lehoczki A, Gesztelyi R, Juhász B, Szilvássy Z, Varga B. Effects of voluntary and forced physical exercise on the retinal health of aging Wistar rats. GeroScience 2024; 46:4707-4728. [PMID: 38795184 PMCID: PMC11336036 DOI: 10.1007/s11357-024-01208-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 05/13/2024] [Indexed: 05/27/2024] Open
Abstract
Aging is accompanied by an increased prevalence of degenerative conditions, including those affecting ocular health, which significantly impact quality of life and increase the burden on healthcare systems. Among these, retinal aging is of particular concern due to its direct link to vision impairment, a leading cause of disability in the elderly. Vision loss in the aging population is associated with heightened risks of cognitive decline, social isolation, and morbidity. This study addresses the critical gap in our understanding of modifiable lifestyle factors, such as physical exercise, that may mitigate retinal aging and its related pathologies. We investigated the effects of different exercise regimens-voluntary (recreational-type) and forced (high-intensity)-on the retinal health of aging Wistar rats (18-month-old), serving as a model for studying the translational potential of exercise interventions in humans. Male Wistar rats were divided into four groups: a young control (3-month-old) for baseline comparison, an aged sedentary control, an aged group engaging in voluntary exercise via a running wheel in their cage, and an aged group subjected to forced exercise on a treadmill for six sessions of 20 min each per week. After a 6-month experimental period, we assessed retinal function via electroretinography (ERG), measured retinal thickness histologically, and analyzed protein expression changes relevant to oxidative stress, inflammation, and anti-aging mechanisms. Our findings reveal that voluntary exercise positively impacts retinal function and morphology, reducing oxidative stress and inflammation markers while enhancing anti-aging protein expression. In contrast, forced exercise showed diminished benefits. These insights underscore the importance of exercise intensity and preference in preserving retinal health during aging. The study highlights the potential of recreational physical activity as a non-invasive strategy to counteract retinal aging, advocating for further research into exercise regimens as preventative therapies for age-related ocular degenerations.
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Affiliation(s)
- Anna Szilágyi
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Barbara Takács
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Réka Szekeres
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Vera Tarjányi
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Dávid Nagy
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Dániel Priksz
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Mariann Bombicz
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Rita Kiss
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Adrienn Mónika Szabó
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Andrea Lehoczki
- Departments of Hematology and Stem Cell Transplantation, South Pest Central Hospital, National Institute of Hematology and Infectious Diseases, Saint Ladislaus Campus, Budapest, Hungary
- Department of Public Health, Semmelweis University, Budapest, Hungary
- Doctoral College, Health Sciences Program, Semmelweis University, Budapest, Hungary
| | - Rudolf Gesztelyi
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Béla Juhász
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Zoltán Szilvássy
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary
| | - Balázs Varga
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98., 4032, Debrecen, Hungary.
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King C, Rogers LG, Jansen J, Sivayokan B, Neyhard J, Warnes E, Hall SE, Plakke B. Adolescent treadmill exercise enhances hippocampal brain-derived neurotrophic factor (BDNF) expression and improves cognition in autism-modeled rats. Physiol Behav 2024; 284:114638. [PMID: 39004196 PMCID: PMC12032843 DOI: 10.1016/j.physbeh.2024.114638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 06/27/2024] [Accepted: 07/09/2024] [Indexed: 07/16/2024]
Abstract
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by repetitive behaviors and altered communication abilities. Exercise is a low-cost intervention that could improve cognitive function and improve brain plasticity mechanisms. Here, the valproic acid (VPA) model was utilized to induce ASD-like phenotypes in rodents. Animals were exercised on a treadmill and performance was evaluated on a cognitive flexibility task. Biomarkers related to exercise and plasticity regulation were quantified from the prefrontal cortex, hippocampus, and skeletal muscle. Exercised VPA animals had higher levels of hippocampal BDNF compared to sedentary VPA animals and upregulated antioxidant enzyme expression in skeletal muscle. Cognitive improvements were demonstrated in both sexes, but in different domains of cognitive flexibility. This research demonstrates the benefits of exercise and provides evidence that molecular responses to exercise occur in both the central nervous system and in the periphery. These results suggest that improving regulation of BDNF via exercise, even at low intensity, could provide better synaptic regulation and cognitive benefits for individuals with ASD.
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Affiliation(s)
- Cole King
- Department of Psychological Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Liza G Rogers
- Anatomy and Physiology, Kansas State University, Manhattan, KS, 66506, USA
| | - Jeremy Jansen
- Department of Psychological Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Bhavana Sivayokan
- Department of Psychological Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Jenna Neyhard
- Department of Psychological Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Ellie Warnes
- Department of Psychological Sciences, Kansas State University, Manhattan, KS, 66506, USA
| | - Stephanie E Hall
- Anatomy and Physiology, Kansas State University, Manhattan, KS, 66506, USA
| | - Bethany Plakke
- Department of Psychological Sciences, Kansas State University, Manhattan, KS, 66506, USA.
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Lotfi A, Abbasi M, Karami N, Arghavanfar H, Kazeminasab F, Rosenkranz SK. Effects of treadmill training on myelin proteomic markers and cerebellum morphology in a rat model of cuprizone-induced toxic demyelination. J Neuroimmunol 2024; 387:578286. [PMID: 38215583 DOI: 10.1016/j.jneuroim.2024.578286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 01/05/2024] [Accepted: 01/06/2024] [Indexed: 01/14/2024]
Abstract
BACKGROUND Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). If demyelination is persistent, it will result in irreversible axonal injury and loss. The purpose of the current study was to investigate the effects of treadmill training on myelin proteomic markers and cerebellum morphology in a rat model of cuprizone-induced toxic demyelination. METHODS Thirty male rats were randomly assigned to five groups (n = 6 per group), consisting of a healthy control group (Control), a cuprizone (CPZ) group, and three exercise training groups: exercise training before and during the CPZ administration (EX-CPZ-EX), exercise training before the CPZ administration (EX-CPZ), and exercise training during the CPZ administration (CPZ-EX). A rat model of CPZ-induced toxic demyelination consisted of feeding the rats cuprizone pellets (0.2%) for 6 weeks. All exercise groups performed a treadmill training protocol 5 days/week for 6 weeks. Levels of Myelin proteolipid protein (PLP), Myelin oligodendrocyte glycoprotein (MOG), axonal injury in the cerebellar tissue, and volume, weight, and length of the cerebellum were determined. RESULTS Results indicated a significant decrease in PLP and MOG in the CPZ groups compared to the Control group (****p < 0.0001). There was a significant increase in PLP and MOG and a significant decrease in axonal injury in the EX-CPZ-EX group as compared to other CPZ groups (****p < 0.0001), and CPZ-MS and CPZ-EX were not significantly different from one another. However, there were no significant differences between the groups for the volume, weight, or length of the cerebellum. CONCLUSION Treadmill training improved myelin sheath structural proteins and axonal injury in cerebellar tissue in a rat model of CPZ-induced toxic demyelination.
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Affiliation(s)
- Alireza Lotfi
- Department of Exercise Physiology, Ilam Branch, Islamic Azad University, Ilam, Iran
| | - Maryam Abbasi
- Department of Exercise Physiology, Ilam Branch, Islamic Azad University, Ilam, Iran.
| | - Nasrin Karami
- Department of Exercise Physiology, Ilam Branch, Islamic Azad University, Ilam, Iran
| | - Hadis Arghavanfar
- Department of Exercise Physiology, Ilam Branch, Islamic Azad University, Ilam, Iran
| | - Fatemeh Kazeminasab
- Department of Physical Education and Sport Sciences, Faculty of Humanities, University of Kashan, Kashan, Iran
| | - Sara K Rosenkranz
- Department of Kinesiology and Nutrition Sciences, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA
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Parnow A, Hafedh M, Tsunoda I, Patel DI, Baker JS, Saeidi A, Bagchi S, Sengupta P, Dutta S, Łuszczki E, Stolarczyk A, Oleksy Ł, Al Kiyumi MH, Laher I, Zouhal H. Effectiveness of exercise interventions in animal models of multiple sclerosis. Front Med (Lausanne) 2023; 10:1143766. [PMID: 37089595 PMCID: PMC10116993 DOI: 10.3389/fmed.2023.1143766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/03/2023] [Indexed: 04/03/2023] Open
Abstract
Multiple sclerosis (MS) is associated with an impaired immune system that severely affects the spinal cord and brain, and which is marked by progressive inflammatory demyelination. Patients with MS may benefit from exercise training as a suggested course of treatment. The most commonly used animal models of studies on MS are experimental autoimmune/allergic encephalomyelitis (EAE) models. The present review intends to concisely discuss the interventions using EAE models to understand the effectiveness of exercise as treatment for MS patients and thereby provide clear perspective for future research and MS management. For the present literature review, relevant published articles on EAE animal models that reported the impacts of exercise on MS, were extracted from various databases. Existing literature support the concept that an exercise regimen can reduce the severity of some of the clinical manifestations of EAE, including neurological signs, motor function, pain, and cognitive deficits. Further results demonstrate the mechanisms of EAE suppression with information relating to the immune system, demyelination, regeneration, and exercise in EAE. The role for neurotrophic factors has also been investigated. Analyzing the existing reports, this literature review infers that EAE is a suitable animal model that can help researchers develop further understanding and treatments for MS. Besides, findings from previous animal studies supports the contention that exercise assists in ameliorating MS progression.
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Affiliation(s)
- Abdolhossein Parnow
- Department of Sport Biological Sciences, Physical Education and Sports Sciences Faculty, Razi University, Kermanshah, Iran
| | - Muthanna Hafedh
- Department of Exercise Physiology, General Directorate of Education Basrah, Basrah, Iraq
- Department of Sports Activities, College of Adm&Eco/Qurna, University of Basrah, Basrah, Iraq
| | - Ikuo Tsunoda
- Department of Microbiology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Darpan I. Patel
- School of Nursing, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Julien S. Baker
- Department of Sport, Physical Education and Health, Centre for Health and Exercise Science Research, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China
| | - Ayoub Saeidi
- Department of Physical Education and Sport Sciences, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Iran
| | - Sovan Bagchi
- Department of Biomedical Sciences, Gulf Medical University, Ajman, United Arab Emirates
| | - Pallav Sengupta
- Department of Biomedical Sciences, Gulf Medical University, Ajman, United Arab Emirates
| | - Sulagna Dutta
- School of Medical Sciences, Bharath Institute of Higher Education and Research (BIHER), Chennai, India
| | - Edyta Łuszczki
- Institute of Health Sciences, Medical College of Rzeszów University, Rzeszów, Poland
| | - Artur Stolarczyk
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, Warsaw, Poland
| | - Łukasz Oleksy
- Department of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland
| | - Maisa Hamed Al Kiyumi
- Department of Family Medicine and Public Health, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman
| | - Ismail Laher
- Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC, Canada
| | - Hassane Zouhal
- University of Rennes, M2S (Laboratoire Mouvement, Sport, Santé) - EA 1274, Rennes, France
- Institute International des Sciences du Sport (2I2S), Irodouër, France
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Sangüesa G, Batlle M, Muñoz-Moreno E, Soria G, Alcarraz A, Rubies C, Sitjà-Roqueta L, Solana E, Martínez-Heras E, Meza-Ramos A, Amaro S, Llufriu S, Mont L, Guasch E. Intense long-term training impairs brain health compared with moderate exercise: Experimental evidence and mechanisms. Ann N Y Acad Sci 2022; 1518:282-298. [PMID: 36256544 PMCID: PMC10092505 DOI: 10.1111/nyas.14912] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The consequences of extremely intense long-term exercise for brain health remain unknown. We studied the effects of strenuous exercise on brain structure and function, its dose-response relationship, and mechanisms in a rat model of endurance training. Five-week-old male Wistar rats were assigned to moderate (MOD) or intense (INT) exercise or a sedentary (SED) group for 16 weeks. MOD rats showed the highest motivation and learning capacity in operant conditioning experiments; SED and INT presented similar results. In vivo MRI demonstrated enhanced global and regional connectivity efficiency and clustering as well as a higher cerebral blood flow (CBF) in MOD but not INT rats compared with SED. In the cortex, downregulation of oxidative phosphorylation complex IV and AMPK activation denoted mitochondrial dysfunction in INT rats. An imbalance in cortical antioxidant capacity was found between MOD and INT rats. The MOD group showed the lowest hippocampal brain-derived neurotrophic factor levels. The mRNA and protein levels of inflammatory markers were similar in all groups. In conclusion, strenuous long-term exercise yields a lesser improvement in learning ability than moderate exercise. Blunting of MOD-induced improvements in CBF and connectivity efficiency, accompanied by impaired mitochondrial energetics and, possibly, transient local oxidative stress, may underlie the findings in intensively trained rats.
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Affiliation(s)
- Gemma Sangüesa
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red - Cardiovascular (CIBERCV), Madrid, Spain
| | - Montserrat Batlle
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red - Cardiovascular (CIBERCV), Madrid, Spain
| | - Emma Muñoz-Moreno
- Experimental 7T MRI Unit, Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - Guadalupe Soria
- Experimental 7T MRI Unit, Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Laboratory of Surgical Neuroanatomy, Faculty of Medicine and Health Sciences, Institute of Neurosciences, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Anna Alcarraz
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Cira Rubies
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
| | - Laia Sitjà-Roqueta
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Department of Biomedical Sciences, Institute of Neurosciences, School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Elisabeth Solana
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Center of Neuroimmunology, Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Eloy Martínez-Heras
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Center of Neuroimmunology, Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Aline Meza-Ramos
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico City, Mexico.,Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Sergi Amaro
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Comprehensive Stroke Center, Institute of Neurosciences, Hospital Clínic, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Sara Llufriu
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Center of Neuroimmunology, Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM), Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Lluís Mont
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red - Cardiovascular (CIBERCV), Madrid, Spain.,Cardiovascular Institute, Clínic de Barcelona, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Eduard Guasch
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.,Centro de Investigación Biomédica en Red - Cardiovascular (CIBERCV), Madrid, Spain.,Cardiovascular Institute, Clínic de Barcelona, Universitat de Barcelona, Barcelona, Catalonia, Spain.,Departament de Medicina, Facultat de Medicina seu Casanova, Universitat de Barcelona, Barcelona, Catalonia, Spain
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10
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Ferrer-Pérez C, Reguilón MD, Miñarro J, Rodríguez-Arias M. Effect of Voluntary Wheel-Running Exercise on the Endocrine and Inflammatory Response to Social Stress: Conditioned Rewarding Effects of Cocaine. Biomedicines 2022; 10:biomedicines10102373. [PMID: 36289635 PMCID: PMC9598819 DOI: 10.3390/biomedicines10102373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/08/2022] [Accepted: 09/17/2022] [Indexed: 11/21/2022] Open
Abstract
The present paper evaluates the effect of physical activity on the increase of the conditioned rewarding effects of cocaine induced by intermittent social stress and on the neuroinflammatory response that contributes to the enhancement of drug response. For that purpose, three studies were designed in which social stress was induced in different samples of mice through a social-defeat protocol; the mice underwent an increase of physical activity by different modalities of voluntary wheel running (continuous and intermittent access). The results showed that continuous access to running wheels prior to stress enhanced the establishment of cocaine place preference, whereas an intermittent access exerted a protective effect. Wheel running contingent to cocaine administration prevented the development of conditioned preference, and if applied during the extinction of drug memories, it exerted a dual effect depending on the stress background of the animal. Our biological analysis revealed that increased sensitivity to cocaine may be related to the fact that wheel running promotes inflammation though the increase of IL-6 and BDNF levels. Together, these results highlight that physical exercise deeply impacts the organism’s response to stress and cocaine, and these effects should be taken into consideration in the design of a physical intervention.
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Affiliation(s)
- Carmen Ferrer-Pérez
- Department of Psychology and Sociology, Faculty of Humanities and Social Sciences, University of Zaragoza, 44003 Teruel, Spain
| | - Marina D. Reguilón
- Department of Psychobiology, Faculty of Psychology, Universitat de València, 46010 Valencia, Spain
| | - José Miñarro
- Department of Psychobiology, Faculty of Psychology, Universitat de València, 46010 Valencia, Spain
| | - Marta Rodríguez-Arias
- Department of Psychobiology, Faculty of Psychology, Universitat de València, 46010 Valencia, Spain
- Correspondence:
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11
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Exercise training improves memory and produces changes in the adrenal gland morphology in the experimental autoimmune encephalomyelitis. Endocr Regul 2022; 56:31-37. [PMID: 35180820 DOI: 10.2478/enr-2022-0004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Objective. The present study sought to verify the effects of an exercise training on the memory along with the morphological assessment of the adrenal gland tissue in the rats with experimental autoimmune encephalomyelitis (EAE). Methods. Female Lewis rats were randomly divided into three groups: EAE group, EAE group with exercise (EAE+Ex), and control group (CO). Each group contained 10 rats. To evaluate the memory, all rats were subjected to the Morris water maze learning test for four consecutive days and one day for a prop test. EAE was induced by guinea pig spinal cord homogenate emulsified in incomplete Freund's adjuvant and heat-mycobacterium. The exercise training on a motorized treadmill was initiated 3 weeks before EAE induction and disconnected 2 weeks post-induction. Results. We found that exercise training for five weeks produced an improved swimming velocity related to memory improvement in EAE+Ex group in comparison with EAE group, but not an incurable adrenal gland tissue after EAE induction. Conclusions. The experimental design selected for this study appears to be an effective treatment for memory in rats with experimental autoimmune encephalomyelitis.
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12
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Bivona JJ, Poynter ME. An open-source, lockable mouse wheel for the accessible implementation of time- and distance-limited elective exercise. PLoS One 2021; 16:e0261618. [PMID: 34932607 PMCID: PMC8691618 DOI: 10.1371/journal.pone.0261618] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 12/06/2021] [Indexed: 11/18/2022] Open
Abstract
Current methods of small animal exercise involve either voluntary (wheel running) or forced (treadmill running) protocols. Although commonly used, each have several drawbacks which cause hesitancy to adopt these methods. While mice will instinctively run on a wheel, the distance and time spent running can vary widely. Forced exercise, while controllable, puts animals in stressful environments in which they are confined and often shocked for "encouragement." Additionally, both methods require expensive equipment and software, which limit these experiments to well-funded laboratories. To counter these issues, we developed a non-invasive mouse running device aimed to reduce handler-induced stress, provide time- and distance-based stopping conditions, and enable investigators with limited resources to easily produce and use the device. The Lockable Open-Source Training-Wheel (LOST-Wheel) was designed to be 3D printed on any standard entry-level printer and assembled using a few common tools for around 20 USD. It features an on-board screen and is capable of tracking distances, running time, and velocities of mice. The LOST-Wheel overcomes the largest drawback to voluntary exercise, which is the inability to control when and how long mice run, using a servo driven mechanism that locks and unlocks the running surface according to the protocol of the investigator. While the LOST-Wheel can be used without a computer connection, we designed an accompanying application to provide scientists with additional analyses. The LOST-Wheel Logger, an R-based application, displays milestones and plots on a user-friendly dashboard. Using the LOST-Wheel, we implemented a timed running experiment that showed distance-dependent decreases in serum myostatin as well as IL-6 gene upregulation in muscle. To make this device accessible, we are releasing the designs, application, and manual in an open-source format. The implementation of the LOST-Wheel and future iterations will improve upon existing murine exercise equipment and research.
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Affiliation(s)
- Joseph J. Bivona
- Department of Medicine and Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, Vermont, United States of America
- Cellular, Molecular, and Biomedical Sciences Doctoral Program, University of Vermont, Burlington, Vermont, United States of America
| | - Matthew E. Poynter
- Department of Medicine and Vermont Lung Center, University of Vermont Larner College of Medicine, Burlington, Vermont, United States of America
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13
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Bei Y, Wang L, Ding R, Che L, Fan Z, Gao W, Liang Q, Lin S, Liu S, Lu X, Shen Y, Wu G, Yang J, Zhang G, Zhao W, Guo L, Xiao J. Animal exercise studies in cardiovascular research: Current knowledge and optimal design-A position paper of the Committee on Cardiac Rehabilitation, Chinese Medical Doctors' Association. JOURNAL OF SPORT AND HEALTH SCIENCE 2021; 10:660-674. [PMID: 34454088 PMCID: PMC8724626 DOI: 10.1016/j.jshs.2021.08.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 05/09/2021] [Accepted: 07/11/2021] [Indexed: 05/02/2023]
Abstract
Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However, the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated. Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection. However, standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective, high-quality animal studies using exercise to prevent and treat cardiovascular diseases. In our review, we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training, emphasizing the appropriate measurements and analysis in these chronic exercise models. We also provide recommendations for optimal design of animal exercise studies in cardiovascular research, including the choice of exercise models, control of exercise protocols, exercise at different stages of disease, and other considerations, such as age, sex, and genetic background. We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases.
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Affiliation(s)
- Yihua Bei
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, School of Medicine, Shanghai University, Nantong 226011, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai 200444, China
| | - Lei Wang
- Department of Rehabilitation Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Rongjing Ding
- Department of Cardiology, Peking University People's Hospital, Beijing 100044, China
| | - Lin Che
- Department of Cardiology, Tongji Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai 200065, China
| | - Zhiqing Fan
- Department of Cardiology, Daqing Oilfield General Hospital, Daqing 163000, China
| | - Wei Gao
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
| | - Qi Liang
- Department of Rehabilitation Medicine, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
| | - Shenghui Lin
- School of Medicine, Huaqiao University, Quanzhou 362021, China
| | - Suixin Liu
- Division of Cardiac Rehabilitation, Department of Physical Medicine and Rehabilitation, Xiangya Hospital of Central South University, Changsha 410008, China
| | - Xiao Lu
- Department of Rehabilitation Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yuqin Shen
- Department of Cardiology, Tongji Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai 200065, China
| | - Guifu Wu
- Department of Cardiology, Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518033, China; Guangdong Innovative Engineering and Technology Research Center for Assisted Circulation, Sun Yat-Sen University, Shenzhen 518033, China; NHC Key Laboratory of Assisted Circulation, Sun Yat-Sen University, Guangzhou 510080, China
| | - Jian Yang
- Department of Rehabilitation Medicine, Shanghai Xuhui Central Hospital, Shanghai 200031, China
| | - Guolin Zhang
- Cardiac Rehabilitation Department, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Wei Zhao
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
| | - Lan Guo
- Cardiac Rehabilitation Department, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
| | - Junjie Xiao
- Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, School of Medicine, Shanghai University, Nantong 226011, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai 200444, China.
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14
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Hafez S, Eid Z, Alabasi S, Darwiche Y, Channaoui S, Hess DC. Mechanisms of Preconditioning Exercise-Induced Neurovascular Protection in Stroke. J Stroke 2021; 23:312-326. [PMID: 34649377 PMCID: PMC8521252 DOI: 10.5853/jos.2020.03006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 09/13/2021] [Indexed: 12/27/2022] Open
Abstract
Ischemic stroke is a leading cause of death and disability. Tissue plasminogen activator is the only U.S. Food and Drug Administration approved thrombolytic therapy for ischemic stroke patients till date. However, its use is limited due to increased risk of bleeding and narrow therapeutic window. Most of the preclinically tested pharmacological agents failed to be translated to the clinic. This drives the need for alternative therapeutic approaches that not only provide enhanced neuroprotection, but also reduce the risk of stroke. Physical exercise is a sort of preconditioning that provides the body with brief ischemic episodes that can protect the body from subsequent severe ischemic attacks like stroke. Physical exercise is known to improve cardiovascular health. However, its role in providing neuroprotection in stroke is not clear. Clinical observational studies showed a correlation between regular physical exercise and reduced risk and severity of ischemic stroke and better outcomes after stroke. However, the underlying mechanisms through which prestroke exercise can reduce the stroke injury and improve the outcomes are not completely understood. The purpose of this review is to: demonstrate the impact of exercise on stroke outcomes and show the potential role of exercise in stroke prevention and recovery; uncover the underlying mechanisms through which exercise reduces the neurovascular injury and improves stroke outcomes aiming to develop novel therapeutic approaches.
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Affiliation(s)
- Sherif Hafez
- Department of Pharmaceutical Sciences, College of Pharmacy Mercer University, Atlanta, GA, USA.,Neurology Department, Augusta University, Augusta, GA, USA
| | - Zeina Eid
- College of Pharmacy Larkin University, Miami, FL, USA
| | - Sara Alabasi
- College of Pharmacy Larkin University, Miami, FL, USA
| | | | | | - David C Hess
- Neurology Department, Augusta University, Augusta, GA, USA
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15
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Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis. Mol Neurobiol 2021; 58:5602-5617. [PMID: 34368932 DOI: 10.1007/s12035-021-02506-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 07/20/2021] [Indexed: 12/31/2022]
Abstract
Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), 14-3-3γ, p-β-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14-3-3γ were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-α, IL-6, IL-1β, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14-3-3γ/p-β-catenin Ser37/Bax/caspase-3 pathway.
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16
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Zhang P, Yang L, Li G, Jin Y, Wu D, Wang QM, Huang P. Agrin Involvement in Synaptogenesis Induced by Exercise in a Rat Model of Experimental Stroke. Neurorehabil Neural Repair 2020; 34:1124-1137. [PMID: 33135566 DOI: 10.1177/1545968320969939] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Agrin is a proteoglycan that aggregates nicotinic acetylcholine receptors (AChRs) on neuromuscular junctions and takes part in synaptogenesis in the development of the central nervous system. However, its effects on neural repair and synaptogenesis after stroke are still unclear. OBJECTIVE This study aimed to investigate the effects of agrin on neural repair and synaptogenesis after stroke and the effects of exercise on this process in vivo and in vitro. METHODS Exercise with gradually increased intensity was initiated at 1 day after middle cerebral artery occlusion (MCAO) for a maximum of 14 days. Neurological deficit scores and foot fault tests were used to assess the behavioral recovery. Western blotting, immunofluorescence, and electron microscopic images were used to detect the expression of agrin, synaptogenesis-related proteins, and synaptic density in vivo. In vitro, the ischemic neuron model was established via oxygen-glucose deprivation (OGD). The lentivirus overexpressed agrin and CREB inhibitor were used to investigate the mechanism by which agrin promoted synaptogenesis. RESULTS Exercise promoted behavioral recovery and this beneficial role was linked to the upregulated expression of agrin and increased synaptic density. Overexpressed agrin promoted synaptogenesis in OGD neuron, CREB inhibitor downregulated the expression of agrin and hampered synaptogenesis in cultured neurons. CONCLUSIONS These results indicated that exercise poststroke improved the recovery of behavioral function after stroke. Synaptogenesis was an important and beneficial factor, and agrin played a critical role in this process and could be a potential therapeutic target for the treatment of stroke and other nervous system diseases.
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Affiliation(s)
- Pengyue Zhang
- Yunnan University of Traditional Chinese Medicine, Kunming, China.,Kunming University of Science and Technology, Kunming, China
| | - Liqiang Yang
- Kunming University of Science and Technology, Kunming, China
| | - Guangxiang Li
- Kunming University of Science and Technology, Kunming, China
| | - Yaju Jin
- Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Danli Wu
- Yunnan University of Traditional Chinese Medicine, Kunming, China
| | - Qing Mei Wang
- Spaulding Rehabilitation Hospital, Charlestown, MA, USA
| | - Peidong Huang
- Yunnan University of Traditional Chinese Medicine, Kunming, China
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17
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Zhang D, Lu Y, Zhao X, Zhang Q, Li L. Aerobic exercise attenuates neurodegeneration and promotes functional recovery - Why it matters for neurorehabilitation & neural repair. Neurochem Int 2020; 141:104862. [PMID: 33031857 DOI: 10.1016/j.neuint.2020.104862] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 09/28/2020] [Accepted: 09/29/2020] [Indexed: 12/19/2022]
Abstract
Aerobic exercise facilitates optimal neurological function and exerts beneficial effects in neurologic injuries. Both animal and clinical studies have shown that aerobic exercise reduces brain lesion volume and improves multiple aspects of cognition and motor function after stroke. Studies using animal models have proposed a wide range of potential molecular mechanisms that underlie the neurological benefits of aerobic exercise. Furthermore, additional exercise parameters, including time of initiation, exercise dosage (exercise duration and intensity), and treatment modality are also critical for clinical application, as identifying the optimal combination of parameters will afford patients with maximal functional gains. To clarify these issues, the current review summarizes the known neurological benefits of aerobic exercise under both physiological and pathological conditions and then considers the molecular mechanisms underlying these benefits in the contexts of stroke-like focal cerebral ischemia and cardiac arrest-induced global cerebral ischemia. In addition, we explore the key roles of exercise parameters on the extent of aerobic exercise-induced neurological benefits to elucidate the optimal combination for aerobic exercise intervention. Finally, the current challenges for aerobic exercise implementation after stroke are discussed.
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Affiliation(s)
- Dandan Zhang
- Department of General Practice & Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China
| | - Yujiao Lu
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA
| | - Xudong Zhao
- Department of General Practice & Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China
| | - Quanguang Zhang
- Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.
| | - Lei Li
- Department of General Practice & Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China.
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18
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Wang YL, Cheng JC, Chang CP, Su FC, Chen CC. Individualized Running Wheel System with a Dynamically Adjustable Exercise Area and Speed for Rats Following Ischemic Stroke. Med Sci Monit 2020; 26:e924411. [PMID: 32886655 PMCID: PMC7491243 DOI: 10.12659/msm.924411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Background An innovative animal running wheel with an individualized design was implemented for the rehabilitation of rats following ischemic stroke. Material/Methods The design of the running wheel platform included the running wheel and a side plate for exercise area adjustments. A U-curve with a width of 2 cm was drawn on the lower half of the side plate for the dynamic adjustments of five infrared (IR) sensors based on the physical fitness of the rats. The individualized training process for this running wheel consisted of 2 days of free training to record their average and maximum speeds, 3 days of progressive training to determine their exercise areas, and 2 weeks of normal training based on their average speeds, maximum speeds, and exercise areas. Blood samples were obtained from the tail veins of all rats before the operations and on Days 14, 21, and 28 postsurgery to measure cortisol levels. The motor function tests were performed on Days 7 and 28 postsurgery. On Day 28 postsurgery, the rats were sacrificed under anesthesia, and their brains were removed for Nissl and H&E staining. Results On Day 28 after surgery, the motor function, lesion volume, and cell damage of the DEARW and control groups differed significantly, indicating that this device is effective for stroke rehabilitation. Conclusions The outcomes of the rats that were rehabilitated using the newly designed training system were better than those of their control-group counterparts, indicating the advantages of this designed system.
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Affiliation(s)
- Yu-Lin Wang
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.,Center of General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan.,Department of Physical Medicine and Rehabilitation, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jui-Chi Cheng
- Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, Taiwan
| | - Ching-Ping Chang
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Fong-Chin Su
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
| | - Chi-Chun Chen
- Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, Taiwan
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19
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Chen CC, Chang CP. Development of a three-channel automatic climbing training system for rat rehabilitation after ischemic stroke. ACTA ACUST UNITED AC 2020; 53:e8943. [PMID: 32555931 PMCID: PMC7296713 DOI: 10.1590/1414-431x20208943] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 04/16/2020] [Indexed: 01/21/2023]
Abstract
This paper reports the development of a three-channel automatic speed-matching climbing training system that could train three rats at the same time for rehabilitation after an ischemic stroke. An infrared (IR) remote sensor was installed at the end of each channel to monitor the real-time position of a climbing rat. This research was carried out in five stages: i) system design; ii) hardware circuit; iii) running speed control; iv) functional testing; and v) verification using an animal model of cerebral stroke. The rehabilitated group significantly outperformed the middle cerebral artery occlusion (MCAo) sedentary group in the rota-rod and inclined plate tests 21 days after a stroke. The rehabilitated group also had a cerebral infarction volume of 28.34±19.4%, far below 56.81±18.12% of the MCAo group 28 days after the stroke, validating the effectiveness of this training platform for stroke rehabilitation. The running speed of the climbing rehabilitation training platform was designed to adapt to the physical conditions of subjects, and overtraining injuries can be completely prevented accordingly.
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Affiliation(s)
- Chi-Chun Chen
- Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, Taiwan
| | - Ching-Ping Chang
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
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20
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Toval A, Vicente-Conesa F, Martínez-Ortega P, Kutsenko Y, Morales-Delgado N, Garrigos D, Alonso A, Ribeiro Do Couto B, Popović M, Ferran JL. Hypothalamic Crh/ Avp, Plasmatic Glucose and Lactate Remain Unchanged During Habituation to Forced Exercise. Front Physiol 2020; 11:410. [PMID: 32499715 PMCID: PMC7243680 DOI: 10.3389/fphys.2020.00410] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Accepted: 04/06/2020] [Indexed: 12/14/2022] Open
Abstract
It has been demonstrated that physical activity contributes to a healthier life. However, there is a knowledge gap regarding the neural mechanisms producing these effects. One of the keystones to deal with this problem is to use training programs with equal loads of physical activity. However, irregular motor and stress responses have been found in murine exercise models. Habituation to forced exercise facilitates a complete response to a training program in all rodents, reaching the same load of physical activity among animals. Here, it was evaluated if glucose and lactate - which are stress biomarkers - are increased during the habituation to exercise. Sprague-Dawley rats received an 8-days habituation protocol with progressive increments of time and speed of running. Then, experimental and control (non-habituated) rats were subjected to an incremental test. Blood samples were obtained to determine plasmatic glucose and lactate levels before, immediately after and 30 min after each session of training. Crh and Avp mRNA expression was determined by two-step qPCR. Our results revealed that glucose and lactate levels are not increased during the habituation period and tend to decrease toward the end of the protocol. Also, Crh and Avp were not chronically activated by the habituation program. Lactate and glucose, determined after the incremental test, were higher in control rats without previous contact with the wheel, compared with habituated and wheel control rats. These results suggest that the implementation of an adaptive phase prior to forced exercise programs might avoid non-specific stress responses.
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Affiliation(s)
- Angel Toval
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
| | - Francisco Vicente-Conesa
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
| | - Paloma Martínez-Ortega
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
| | - Yevheniy Kutsenko
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
| | - Nicanor Morales-Delgado
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain.,Department of Histology and Anatomy, Faculty of Medicine, University of Miguel Hernández, Sant Joan d'Alacant, Spain
| | - Daniel Garrigos
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
| | - Antonia Alonso
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
| | - Bruno Ribeiro Do Couto
- Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain.,Department of Human Anatomy and Psychobiology, Faculty of Psychology, University of Murcia, Murcia, Spain
| | - Miroljub Popović
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
| | - José Luis Ferran
- Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Spain.,Institute of Biomedical Research of Murcia, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, Spain
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21
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de Abreu MS, Giacomini ACVV, Genario R, Rech N, Carboni J, Lakstygal AM, Amstislavskaya TG, Demin KA, Leonard BE, Vlok M, Harvey BH, Piato A, Barcellos LJG, Kalueff AV. Non-pharmacological and pharmacological approaches for psychiatric disorders: Re-appraisal and insights from zebrafish models. Pharmacol Biochem Behav 2020; 193:172928. [PMID: 32289330 DOI: 10.1016/j.pbb.2020.172928] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 04/07/2020] [Indexed: 12/11/2022]
Abstract
Acute and chronic stressors are common triggers of human mental illnesses. Experimental animal models and their cross-species translation to humans are critical for understanding of the pathogenesis of stress-related psychiatric disorders. Mounting evidence suggests that both pharmacological and non-pharmacological approaches can be efficient in treating these disorders. Here, we analyze human, rodent and zebrafish (Danio rerio) data to compare the impact of non-pharmacological and pharmacological therapies of stress-related psychopathologies. Emphasizing the likely synergism and interplay between pharmacological and environmental factors in mitigating daily stress both clinically and in experimental models, we argue that environmental enrichment emerges as a promising complementary therapy for stress-induced disorders across taxa. We also call for a broader use of novel model organisms, such as zebrafish, to study such treatments and their potential interplay.
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Affiliation(s)
- Murilo S de Abreu
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, USA.
| | - Ana C V V Giacomini
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil; Postgraduate Program in Environmental Sciences, University of Passo Fundo (UPF), Passo Fundo, Brazil
| | - Rafael Genario
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil
| | - Nathália Rech
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil
| | - Júlia Carboni
- Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil
| | - Anton M Lakstygal
- Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Center, St. Petersburg, Russia; Granov Russian Scientific Center of Radiology and Surgical Technologies, St. Petersburg, Russia
| | - Tamara G Amstislavskaya
- Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk, Russia; Institute of Medicine and Psychology, Novosibirsk State University, Novosibirsk, Russia
| | - Konstantin A Demin
- Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia; Institute of Experimental Medicine, Almazov National Medical Research Center, St. Petersburg, Russia
| | - Brian E Leonard
- University College Galway, Pharmacology Department, Galway, Ireland
| | - Marli Vlok
- Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Potchefstroom, South Africa
| | - Brian H Harvey
- Center of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Potchefstroom, South Africa
| | - Angelo Piato
- The International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, USA; Postgraduate Program in Neurosciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Leonardo J G Barcellos
- Postgraduate Program in Environmental Sciences, University of Passo Fundo (UPF), Passo Fundo, Brazil; Postgraduate Program in Bio-Experimentation, University of Passo Fundo (UPF), Passo Fundo, Brazil; Postgraduate Program in Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, Brazil
| | - Allan V Kalueff
- School of Pharmacy, Southwest University, Chongqing, China; Ural Federal University, Ekaterinburg, Russia.
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22
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Holschneider DP, Wang Z, Guo Y, Sanford MT, Yeh J, Mao JJ, Zhang R, Rodriguez LV. Exercise modulates neuronal activation in the micturition circuit of chronically stressed rats: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study. Physiol Behav 2020; 215:112796. [PMID: 31884113 PMCID: PMC7269603 DOI: 10.1016/j.physbeh.2019.112796] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/26/2019] [Accepted: 12/26/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Rats exposed to water avoidance stress (WAS) show increased urinary frequency, increased somatosensory nociceptive reflex responses, as well as altered brain responses to bladder distension, analogous to similar observations made in patients with urologic chronic pelvic pain syndrome (UCPPS). Exercise has been proposed as a potential treatment option for patients with chronic urinary frequency and urgency. We examined the effects of exercise on urinary voiding parameters and functional brain activation during bladder distension in rats exposed to WAS. METHODS Adult, female Wistar Kyoto rats were exposed to 10 days of WAS and thereafter randomized to either voluntary exercise for 3 weeks or sedentary groups. Voiding parameters were assessed at baseline, post-WAS, and weekly for 3 weeks. Thereafter, cerebral blood flow (CBF) mapping was performed during isotonic bladder distension (20 cm H2O) after intravenous bolus injection of [14C]-iodoantipyrine. Regional CBF was quantified in autoradiographs of brain slices and analyzed in 3-D reconstructed brains by statistical parametric mapping. Functional connectivity was examined between regions of the micturition circuit through interregional correlation analysis. RESULTS WAS exposure in sedentary animals (WAS/no-EX) increased voiding frequency and decreased urinary volumes per void. Exercise exposure in WAS animals (WAS/EX) resulted in a progressive decline in voiding frequency back to the baseline, as well as increased urinary volumes per void. Within the micturition circuit, WAS/EX compared to WAS/no-EX demonstrated a significantly lower rCBF response to passive bladder distension in Barrington's nucleus that is part of the spinobulbospinal voiding reflex, as well as in the periaqueductal gray (PAG) which modulates this reflex. Greater rCBF was noted in WAS/EX animals broadly across corticolimbic structures, including the cingulate, medial prefrontal cortex (prelimbic, infralimbic areas), insula, amygdala, and hypothalamus, which provide a 'top-down' decision point where micturition could be inhibited or triggered. WAS/EX showed a significantly greater positive brain functional connectivities compared to WAS/no-EX animals within regions of the extended reflex loop (PAG, Barrington's nucleus, intermediodorsal thalamic nucleus, pons), as well as within regions of the corticolimbic decision-making loop of the micturition circuit, with a strikingly negative correlation between these pathways. Urinary frequency was positively correlated with rCBF in the pons, and negatively correlated with rCBF in the cingulate cortex. CONCLUSION Our results suggest that chronic voluntary exercise may decrease urinary frequency at two points of control in the micturition circuit. During the urine storage phase, it may diminish the influence of the reflex micturition circuit itself, and/or it may increase corticolimbic control of voiding. Exercise may be an effective adjunct therapeutic intervention for modifying the urinary symptoms in patients with UCPPS.
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Affiliation(s)
- Daniel P Holschneider
- Departments of Psychiatry and the Behavioral Sciences, Los Angeles, CA, United States.
| | - Zhuo Wang
- Departments of Psychiatry and the Behavioral Sciences, Los Angeles, CA, United States
| | - Yumei Guo
- Departments of Psychiatry and the Behavioral Sciences, Los Angeles, CA, United States
| | - Melissa T Sanford
- Urology at the University of Southern California, Los Angeles, CA, United States
| | - Jihchao Yeh
- Urology at the University of Southern California, Los Angeles, CA, United States
| | - Jackie J Mao
- Urology at the University of Southern California, Los Angeles, CA, United States
| | - Rong Zhang
- Urology at the University of Southern California, Los Angeles, CA, United States
| | - Larissa V Rodriguez
- Urology at the University of Southern California, Los Angeles, CA, United States.
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23
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Running exercise protects oligodendrocytes in the medial prefrontal cortex in chronic unpredictable stress rat model. Transl Psychiatry 2019; 9:322. [PMID: 31780641 PMCID: PMC6882819 DOI: 10.1038/s41398-019-0662-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 11/05/2019] [Accepted: 11/08/2019] [Indexed: 12/28/2022] Open
Abstract
Previous postmortem and animal studies have shown decreases in the prefrontal cortex (PFC) volume and the number of glial cells in the PFC of depression. Running exercise has been shown to alleviate depressive symptoms. However, the effects of running exercise on the medial prefrontal cortex (mPFC) volume and oligodendrocytes in the mPFC of depressed patients and animals have not been investigated. To address these issues, adult male rats were subjected to chronic unpredictable stress (CUS) for 5 weeks, followed by treadmill running for 6 weeks. Then, the mPFC volume and the mPFC oligodendrocytes were investigated using stereology, immunohistochemistry, immunofluorescence and western blotting. Using a CUS paradigm that allowed for the analysis of anhedonia, we found that running exercise alleviated the deficits in sucrose preference, as well as the decrease in the mPFC volume. Meanwhile, we found that running exercise significantly increased the number of CNPase+ oligodendrocytes and Olig2+ oligodendrocytes, reduced the ratio between Olig2+/NG2+ oligodendrocytes and Olig2+ oligodendrocytes and increased myelin basic protein (MBP), CNPase and Olig2 protein expression in the mPFC of the CUS rat model. However, running exercise did not change NG2+ oligodendrocyte number in the mPFC in these rats. These results indicated that running exercise promoted the differentiation of oligodendrocytes and myelin-forming ability in the mPFC in the context of depression. These findings suggest that the beneficial effects of running exercise on mPFC volume and oligodendrocytes in mPFC might be an important structural basis for the antidepressant effects of running exercise.
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24
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Venezia AC, Hyer MM, Glasper ER, Roth SM, Quinlan EM. Acute forced exercise increases Bdnf IV mRNA and reduces exploratory behavior in C57BL/6J mice. GENES BRAIN AND BEHAVIOR 2019; 19:e12617. [PMID: 31621198 DOI: 10.1111/gbb.12617] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 10/08/2019] [Accepted: 10/10/2019] [Indexed: 12/25/2022]
Abstract
Acute exercise has been shown to improve memory in humans. Potential mechanisms include increased Bdnf expression, noradrenergic activity and modification of glutamate receptors. Because mice are commonly used to study exercise and brain plasticity, it is important to explore how acute exercise impacts behavior in this model. C57BL/6J mice were assigned to three groups: control, moderate-intensity running, and high-intensity running. Control mice were placed on a stationary treadmill for 30 minutes and moderate- and high-intensity mice ran for 30 minutes at 12 and 15-17 m/min, respectively. Mice were sacrificed immediately after running and the hippocampus removed. Total Bdnf, Bdnf exon IV, and glutamate receptor subunits were quantified with quantitative polymerase chain reaction. Total and phosphorylated GluR1 (Ser845 and Ser831) protein was quantified following immunoblotting. Utilizing the same protocol for control and high-intensity running, object location memory was examined in a separate cohort of mice. Anxiety-like behavior was assessed in the open field task (OFT) in a third cohort of mice that were separated into four groups: control-saline, control-DSP-4, acute exercise-saline, and acute exercise-DSP-4. DSP-4 was used to lesion the central noradrenergic system. We observed higher Bdnf IV mRNA in high-intensity runners compared to controls, but no effects of acute exercise on memory. In the OFT, runners traveled less distance and spent more time grooming than controls. DSP-4 did not attenuate the effects of exercise. A single bout of exercise increases Bdnf IV mRNA in an intensity-dependent manner; however, high-intensity running reduces exploratory behavior in C57BL/6J mice.
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Affiliation(s)
- Andrew C Venezia
- Department of Exercise Science and Sport, The University of Scranton, Scranton, Pennsylvania
| | - Molly M Hyer
- Department of Psychology, University of Maryland, College Park, Maryland
| | - Erica R Glasper
- Department of Psychology, University of Maryland, College Park, Maryland
| | - Stephen M Roth
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland
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Taguchi S, Choudhury ME, Miyanishi K, Nakanishi Y, Kameda K, Abe N, Yano H, Yorozuya T, Tanaka J. Aggravating effects of treadmill exercises during the early-onset period in a rat traumatic brain injury model: When should rehabilitation exercises be initiated? IBRO Rep 2019; 7:82-89. [PMID: 31720487 PMCID: PMC6838542 DOI: 10.1016/j.ibror.2019.10.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 10/08/2019] [Indexed: 12/14/2022] Open
Abstract
A traumatic brain injury model was prepared in rats by stab wounding. Rats were forced to walk slowly on a treadmill once for 10 min at 24 h or 48 h after wounding. Exercise, particularly at 24 h, aggravated motor impairment while increasing the expression of proinflammatory factors. Exercise for rehabilitation should be initiated after 48 h of severe brain injury onset. Physical exercise is one of the best interventions for improving traumatic brain injury (TBI) outcomes. However, an argument has been raised regarding the timing at which physical exercise should be initiated. In this study, male Wistar rats were subjected to stab wounding of the right hemisphere to develop a TBI model and were forced to walk once on a treadmill at a 5-m/min pace at 24 h or 48 h after TBI for 10 min. Injured brain tissue was dissected after TBI to evaluate the effects of exercise. Behavioral abnormalities and motor impairment were assessed by various behavioral tests between 2 and 3 weeks after TBI. Exercise did not affect the circulating corticosterone levels and the weight of the adrenal glands. Exercise particularly that at 24 h, worsened the motor impairment of the left forelimbs. Quantitative reverse-transcription polymerase chain reaction showed that exercise at 24 h increased proinflammatory cytokines and chemokines on the third day while suppressing the proinflammatory reactions on the fourth day. Exercise at both time points decreased expression of transforming growth factor (TGF) β1 and its receptor TGFβR1. Exercise at 24 h increased phosphorylation of IκB kinase on the fourth day, which may be correlated with the decreased effects of TGFβ1. Even a low-intensity exercise activity could cause deleterious effects when it is initiated within 48 h after the onset of severe TBI, probably because of the resulting proinflammatory effects. Therefore, rehabilitation exercise programs should be initiated after 48 h of TBI onset.
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Affiliation(s)
- Satoru Taguchi
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
| | - Mohammed E Choudhury
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
| | - Kazuya Miyanishi
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
| | - Yuiko Nakanishi
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
| | - Kenji Kameda
- Advanced Research Support Center, Division of Analytical Bio-Medicine, Ehime University, Toon, Ehime, Japan
| | - Naoki Abe
- Department of Anesthesia and Perioperative Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
| | - Hajime Yano
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
| | - Toshihiro Yorozuya
- Department of Anesthesia and Perioperative Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
| | - Junya Tanaka
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan
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Cohan CH, Youbi M, Saul I, Ruiz AA, Furones CC, Patel P, Perez E, Raval AP, Dave KR, Zhao W, Dong C, Rundek T, Koch S, Sacco RL, Perez-Pinzon MA. Sex-Dependent Differences in Physical Exercise-Mediated Cognitive Recovery Following Middle Cerebral Artery Occlusion in Aged Rats. Front Aging Neurosci 2019; 11:261. [PMID: 31619985 PMCID: PMC6759590 DOI: 10.3389/fnagi.2019.00261] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 09/04/2019] [Indexed: 01/14/2023] Open
Abstract
Stroke remains a leading cause of death and disability in the United States. No current treatments exist to promote cognitive recovery in survivors of stroke. A previous study from our laboratory determined that an acute bout of forced treadmill exercise was able to promote cognitive recovery in 3 month old male rats after middle cerebral artery occlusion (MCAo). In this study, we tested the hypothesis that 6 days of intense acute bout of forced treadmill exercise (physical exercise – PE) promotes cognitive recovery in 11–14 month old male rats. We determined that PE was able to ameliorate cognitive deficits as determined by contextual fear conditioning. Additionally, we also tested the hypothesis that PE promotes cognitive recovery in 11–13 month old reproductive senescent female rats. In contrast to males, the same intensity of exercise that decrease cognitive deficits in males was not able to promote cognitive recovery in female rats. Additionally, we determined that exercise did not lessen infarct volume in both male and female rats. There are many factors that contribute to higher stroke mortality and morbidities in women and thus, future studies will investigate the effects of PE in aged female rats to identify sex differences.
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Affiliation(s)
- Charles H Cohan
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Mehdi Youbi
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Isabel Saul
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Alex A Ruiz
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Concepcion C Furones
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Pujan Patel
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Edwin Perez
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Ami P Raval
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Kunjan R Dave
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Weizhao Zhao
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Chuanhui Dong
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Tatjana Rundek
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Sebastian Koch
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Ralph L Sacco
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Miguel A Perez-Pinzon
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory, Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
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Remarkable cell recovery from cerebral ischemia in rats using an adaptive escalator-based rehabilitation mechanism. PLoS One 2019; 14:e0223820. [PMID: 31603928 PMCID: PMC6788702 DOI: 10.1371/journal.pone.0223820] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 10/01/2019] [Indexed: 12/22/2022] Open
Abstract
Currently, many ischemic stroke patients worldwide suffer from physical and mental impairments, and thus have a low quality of life. However, although rehabilitation is acknowledged as an effective way to recover patients’ health, there does not exist yet an adaptive training platform for animal tests so far. For this sake, this paper aims to develop an adaptive escalator (AE) for rehabilitation of rats with cerebral ischemia. Rats were observed to climb upward spontaneously, and a motor-driven escalator, equipped with a position detection feature and an acceleration/deceleration mechanism, was constructed accordingly as an adaptive training platform. The rehabilitation performance was subsequently rated using an incline test, a rotarod test, the infarction volume, the lesion volume, the number of MAP2 positive cells and the level of cortisol. This paper is presented in 3 parts as follows. Part 1 refers to the escalator mechanism design, part 2 describes the adaptive ladder-climbing rehabilitation mechanism, and part 3 discusses the validation of an ischemic stroke model. As it turned out, a rehabilitated group using this training platform, designated as the AE group, significantly outperformed a control counterpart in terms of a rotarod test. After the sacrifice of the rats, the AE group gave an average infarction volume of (34.36 ± 3.8)%, while the control group gave (66.41 ± 3.1)%, validating the outperformance of the escalator-based rehabilitation platform in a sense. An obvious difference between the presented training platform and conventional counterparts is the platform mechanism, and for the first time in the literature rats can be well and voluntarily rehabilitated at full capacity using an adaptive escalator. Taking into account the physical diversity among rats, the training strength provided was made adaptive as a reliable way to eliminate workout or secondary injury. Accordingly, more convincing arguments can be made using this mental stress-free training platform.
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28
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Rafie F, Sheibani V, Shahbazi M, Naghdi N, Pourranjbar M, Sheikh M. The effects of voluntary exercise on learning and memory deficit in Parkinson’s disease model of rats. SPORT SCIENCES FOR HEALTH 2019. [DOI: 10.1007/s11332-019-00531-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Terashi T, Otsuka S, Takada S, Nakanishi K, Ueda K, Sumizono M, Kikuchi K, Sakakima H. Neuroprotective effects of different frequency preconditioning exercise on neuronal apoptosis after focal brain ischemia in rats. Neurol Res 2019; 41:510-518. [PMID: 30822224 DOI: 10.1080/01616412.2019.1580458] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
OBJECTIVE Preconditioning exercise can exert neuroprotective effects after stroke; however, the effects of exercise intensity, frequency, duration are unknown. We investigated the neuroprotective effect of different frequency preconditioning exercise on neuronal apoptosis after cerebral ischemia in rats. METHODS Rats were divided into the following five groups: 5 times a week of exercise (5/w-Ex) group, 3 times a week of exercise (3/w-Ex) group, once a week of exercise (1/w-Ex) group, no exercise (No-Ex) group, and intact control (control) group. Rats were made to run on a treadmill for 30 min per day at a speed of 25 m/min for 3 weeks. After the running program, the rats were subjected to 60-min left middle cerebral artery occlusion. Two days after ischemia, the cerebral infarct volume, neurological and motor function, Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, expression of caspase-3, and TUNEL positive cells were examined in the cerebral cortex surrounding the ischemic zone. RESULTS The 3/w-Ex and 5/w-Ex groups showed significantly reduced infarct volumes compared with the No-Ex group, but the 1/w-Ex group did not. In addition, the 3/w-Ex and 5/w-Ex groups had improved neurological scores and sensorimotor function compared with the No-Ex group. The Bax/Bcl-2 ratio, expression of caspase-3, and TUNEL-positive cells significantly decreased in the penumbra area in the 3/w-Ex or 5/w-Ex groups compared with the No-Ex group. DISCUSSION Our findings suggested that three times or more per week of high-intensity preconditioning exercise exert neuroprotective effects through the downregulation of the Bax/Bcl-2 ratio and caspase-3 activation after stroke. ABBREVIATIONS TUNEL: terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick and labeling; MCAO:middle cerebral artery occlusion; BAX:Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; TTC: 2,3,5-triphenyltetrazorlium chloride.
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Affiliation(s)
- Takuto Terashi
- a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan
| | - Shotaro Otsuka
- a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan
| | - Seiya Takada
- a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan
| | - Kazuki Nakanishi
- a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan
| | - Koki Ueda
- a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan
| | - Megumi Sumizono
- a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan
| | - Kiyoshi Kikuchi
- b Division of Brain Science, Department of Physiology , Kurume University School of Medicine , Kurume , Japan
| | - Harutoshi Sakakima
- a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan
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30
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Chen CC, Chang CP, Yang CL. An adaptive fall-free rehabilitation mechanism for ischemic stroke rat patients. Sci Rep 2019; 9:984. [PMID: 30700758 PMCID: PMC6353993 DOI: 10.1038/s41598-018-37282-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 12/04/2018] [Indexed: 11/22/2022] Open
Abstract
Today’s commercial forced exercise platforms had been validated not as a well-designed rehabilitation environment for rats with a stroke, for the reason that rat with a stroke cannot take exercise at a constant intensity for a long period of time. In light of this, this work presented an adaptive, fall-free ischemic stroke rehabilitation mechanism in an animal model, which was implemented in an infrared-sensing adaptive feedback control running wheel (IAFCRW) platform. Consequently, rats with a stroke can be safely rehabilitated all the time, and particularly at full capacity for approximately one third of a training duration, in a completely fall-free environment according to individual physical differences by repeated use of an acceleration/deceleration mechanism. The performance of this platform was assessed using an animal ischemic stroke model. The IAFCRW therapy regimen was validated to outperform a treadmill and a conventional running wheel counterpart with respect to the reduction in the neurobehavioral deficits caused by middle cerebral artery occlusion (MCAo). IAFCRW is the first adaptive forced exercise training platform short of electrical stimulation-assistance in the literature, and ischemic stroke rats benefit more in terms of the behavioral tests run at the end of a 3-week rehabilitation program after a stroke thereby.
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Affiliation(s)
- Chi-Chun Chen
- Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, Taiwan.
| | - Ching-Ping Chang
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Chin-Lung Yang
- Department of Electrical Engineering, National Cheng Kung University, Tainan, Taiwan.
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31
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Wang YL, Lin CH, Chen CC, Chang CP, Lin KC, Su FC, Chou W. Exercise Preconditioning Attenuates Neurological Injury by Preserving Old and Newly Formed HSP72-Containing Neurons in Focal Brain Ischemia Rats. Int J Med Sci 2019; 16:675-685. [PMID: 31217735 PMCID: PMC6566739 DOI: 10.7150/ijms.32962] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 04/04/2019] [Indexed: 12/11/2022] Open
Abstract
Background: Exercise preconditioning (EP+) is a useful and important procedure for the prevention of stroke. We aimed to ascertain whether EP+ protects against ischemic brain injury by preserving heat shock protein (HSP) 72-containing neurons in ischemic brain tissues. Methods: Adult male Sprague-Dawley rats (n=240) were used to assess the contribution of HSP72-containing neurons to the neuroprotective effects of EP+ on ischemic brain injury caused by transient middle cerebral artery occlusion. Results: Significant (P<0.05) increases in the percentages of both old HSP72-containing neurons (NeuN+HSP72 double positive cells) (18~20% vs. 40~50%) and newly formed HSP72-containing neurons (BrdU+NeuN+HSP72 triple positive cells); (2~3% vs. 16~20%) after 3 weeks of exercise coincided with significant (P<0.05) reductions in brain ischemia volume (250 mm3 vs. 100 mm3), brain edema (78% vs. 74% brain water content), blood-brain barrier disruption (1.5 μg/g vs. 0.7 μg/g tissue Evans Blue dye extravasation) and neurological motor deficits (neurological severity scores of 12 vs. 6 and maximal angles of 60° vs. 20°) in brain ischemia rats. Reductions in the percentages of both old (from 40~50% to 10~12%) and newly formed (from 18~20% to 5~7%) HSP72-containing neurons by gene silencing with an intracerebral injection of pSUPER small interfering RNA showed a significant (P<0.05) reversal in the neuroprotective outcomes. Our data provide an inverse correlation between the EP+-mediated increases in both old and newly formed HSP72-containing neurons and the extent of cerebral ischemic injury. Conclusions: The percentages of both old and newly formed HSP72-containing neurons are inversely correlated with the outcomes of ischemic brain injury. Additionally, preischemic treadmill exercise improves the outcomes of ischemic brain injury by preserving both the old and newly formed HSP72-containing neurons in rats.
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Affiliation(s)
- Yu-Lin Wang
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.,Center of General Education, Southern Taiwan University of Science and Technology, Tainan, Taiwan.,Department of Physical Medicine and Rehabilitation, Chi-Mei Medical Center, Tainan, Taiwan
| | - Cheng-Hsien Lin
- Department of Medicine, Mackay Medical College, New Taipei, Taiwan
| | - Chi-Chun Chen
- Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, Taiwan
| | - Ching-Ping Chang
- Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan
| | - Kao-Chang Lin
- Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan
| | - Fong-Chin Su
- Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.,Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan
| | - Willy Chou
- Department of Physical Medicine and Rehabilitation, Chi-Mei Medical Center, Tainan, Taiwan.,Department of Recreation and Healthcare Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
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32
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Abstract
PURPOSE OF REVIEW Physical activity is increasingly recommended for chronic pain. In this review, we briefly survey recent, high-quality meta-analyses on the effects of exercise in human chronic pain populations, followed by a critical discussion of the rodent literature. RECENT FINDINGS Most meta-analytical studies on the effects of exercise in human chronic pain populations describe moderate improvements in various types of chronic pain, despite substantial variability in the outcomes reported in the primary literature. The most consistent findings suggest that while greater adherence to exercise programs produces better outcomes, there is minimal support for the superiority of one type of exercise over another. The rodent literature similarly suggests that while regular exercise reduces hypersensitivity in rodent models of chronic pain, exercise benefits do not appear to relate to either the type of injury or any particular facet of the exercise paradigm. Potential factors underlying these results are discussed, including the putative involvement of stress-induced analgesic effects associated with certain types of exercise paradigms. Exercise research using rodent models of chronic pain would benefit from increased attention to the role of stress in exercise-induced analgesia, as well as the incorporation of more clinically relevant exercise paradigms.
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Affiliation(s)
- Mark Henry Pitcher
- Pain and Integrative Neuroscience Laboratory, National Center for Complementary and Integrative Health, National Institutes of Health, Room 1E-420, 35A Convent Drive, Bethesda, MD, 20892, USA.
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33
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Zhao C, Könönen M, Vanninen R, Pitkänen K, Hiekkala S, Jolkkonen J. Translating experimental evidence to finding novel ways to promote motor recovery in stroke patients – a review. Restor Neurol Neurosci 2018; 36:519-533. [PMID: 29889087 DOI: 10.3233/rnn-180814] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
| | | | | | - Kauko Pitkänen
- Brain Research and Rehabilitation Center Neuron, Kuopio, Finland
| | - Sinikka Hiekkala
- Finnish Association of People with Physical Disabilities, Helsinki, Finland
| | - Jukka Jolkkonen
- Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland
- NeuroCenter, Kuopio University Hospital, Kuopio, Finland
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34
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Robison LS, Alessi L, Thanos PK. Chronic forced exercise inhibits stress-induced reinstatement of cocaine conditioned place preference. Behav Brain Res 2018; 353:176-184. [PMID: 30036547 DOI: 10.1016/j.bbr.2018.07.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 06/29/2018] [Accepted: 07/14/2018] [Indexed: 01/04/2023]
Abstract
Stress increases the likelihood of cocaine relapse in humans and animals, even following a prolonged extinction/abstinence period. Exercise has previously been shown to reduce stress and decrease the likelihood of drug dependence, while also reducing cravings in humans and inhibiting relapse behaviors due to other risk factors in rodents. The present study evaluated the efficacy of exercise to reduce stress-induced relapse to cocaine in a rodent model. Young adult female Sprague Dawley rats were tested for cocaine conditioned place preference (CPP), then split into sedentary or exercise (six weeks of one-hour daily treadmill running, five days per week) groups. Following cocaine CPP, rats were tested for extinction behavior, and then tested for stress-primed reinstatement (15 min immobilization) following the six-week intervention period. Exercise inhibited stress-induced reinstatement of cocaine CPP despite increasing serum corticosterone levels following 15 min of immobilization, suggesting that chronic aerobic exercise intervention may result in adaptations of stress pathways. These findings suggest that exercise may help prevent stress-induced drug relapse, adding to a growing body of evidence supporting the utility of exercise to combat substance abuse.
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Affiliation(s)
- Lisa S Robison
- Albany Medical College, Department of Neuroscience and Experimental Therapeutics, 47 New Scotland Ave., Albany, NY, 12208, USA
| | - Luke Alessi
- New York Institute of Technology College of Osteopathic Medicine, 101 Northern Blvd, Glen Head, NY, 11545, USA
| | - Panayotis K Thanos
- University at Buffalo, Research Institute on Addictions, Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, 1021 Main Street, Buffalo, NY, 14203-1016, USA.
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35
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Robison LS, Popescu DL, Anderson ME, Beigelman SI, Fitzgerald SM, Kuzmina AE, Lituma DA, Subzwari S, Michaelos M, Anderson BJ, Van Nostrand WE, Robinson JK. The effects of volume versus intensity of long-term voluntary exercise on physiology and behavior in C57/Bl6 mice. Physiol Behav 2018; 194:218-232. [PMID: 29879399 DOI: 10.1016/j.physbeh.2018.06.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 05/30/2018] [Accepted: 06/01/2018] [Indexed: 12/22/2022]
Abstract
Cardiovascular exercise (CVE) is associated with healthy aging and reduced risk of disease in humans, with similar benefits seen in animals. Most rodent studies, however, have used shorter intervention periods of a few weeks to a few months, begging questions as to the effects of longer-term, or even life-long, exercise. Additionally, most animal studies have utilized a single exercise treatment group - usually unlimited running wheel access - resulting in large volumes of exercise that are not clinically relevant. It is therefore incumbent to determine the physiological and cognitive/behavioral effects of a range of exercise intensities and volumes over a long-term period that model a lifelong commitment to CVE. In the current study, C57/Bl6 mice remained sedentary or were allowed either 1, 3, or 12 h of access to a running wheel per day, 5 days/weeks, beginning at 3.5-4 months of age. Following an eight-month intervention period, animals underwent a battery of behavioral testing, then euthanized and blood and tissue were collected. Longer access to a running wheel resulted in greater volume and higher running speed, but more breaks in running. All exercise groups showed similarly reduced body weight, increased muscle mass, improved motor function on the rotarod, and reduced anxiety in the open field. While all exercise groups showed increased food intake, this was greatest in the 12 h group but did not differ between 1 h and 3 h mice. While exercise dose-dependently increased working memory performance in the y-maze, the 1 h and 12 h groups showed the largest changes in the mass of many organs, as well as alterations in several behaviors including social interaction, novel object recognition, and Barnes maze performance. These findings suggest that long-term exercise has widespread effects on physiology, behavior, and cognition, which vary by "dose" and measure, and that even relatively small amounts of daily exercise can provide benefits.
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Affiliation(s)
- Lisa S Robison
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States.
| | - Dominique L Popescu
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - Maria E Anderson
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - Steven I Beigelman
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - Shannon M Fitzgerald
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - Antonina E Kuzmina
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - David A Lituma
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - Sarima Subzwari
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - Michalis Michaelos
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - Brenda J Anderson
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - William E Van Nostrand
- Department of Neurosurgery, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
| | - John K Robinson
- Department of Psychology, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794, United States
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36
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Geiseler SJ, Morland C. The Janus Face of VEGF in Stroke. Int J Mol Sci 2018; 19:ijms19051362. [PMID: 29734653 PMCID: PMC5983623 DOI: 10.3390/ijms19051362] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/27/2018] [Accepted: 05/01/2018] [Indexed: 12/12/2022] Open
Abstract
The family of vascular endothelial growth factors (VEGFs) are known for their regulation of vascularization. In the brain, VEGFs are important regulators of angiogenesis, neuroprotection and neurogenesis. Dysregulation of VEGFs is involved in a large number of neurodegenerative diseases and acute neurological insults, including stroke. Stroke is the main cause of acquired disabilities, and normally results from an occlusion of a cerebral artery or a hemorrhage, both leading to focal ischemia. Neurons in the ischemic core rapidly undergo necrosis. Cells in the penumbra are exposed to ischemia, but may be rescued if adequate perfusion is restored in time. The neuroprotective and angiogenic effects of VEGFs would theoretically make VEGFs ideal candidates for drug therapy in stroke. However, contradictory to what one might expect, endogenously upregulated levels of VEGF as well as the administration of exogenous VEGF is detrimental in acute stroke. This is probably due to VEGF-mediated blood–brain-barrier breakdown and vascular leakage, leading to edema and increased intracranial pressure as well as neuroinflammation. The key to understanding this Janus face of VEGF function in stroke may lie in the timing; the harmful effect of VEGFs on vessel integrity is transient, as both VEGF preconditioning and increased VEGF after the acute phase has a neuroprotective effect. The present review discusses the multifaceted action of VEGFs in stroke prevention and therapy.
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Affiliation(s)
- Samuel J Geiseler
- Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, 0371 Oslo, Norway.
| | - Cecilie Morland
- Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, 0371 Oslo, Norway.
- Institute for Behavioral Sciences, Faculty of Health Sciences, OsloMet-Oslo Metropolitan University, 0166 Oslo, Norway.
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37
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Gheorghe A, Qiu W, Galea LAM. Hormonal Regulation of Hippocampal Neurogenesis: Implications for Depression and Exercise. Curr Top Behav Neurosci 2018; 43:379-421. [PMID: 30414016 DOI: 10.1007/7854_2018_62] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Adult hippocampal neurogenesis exists in all mammalian species, including humans, and although there has been considerable research investigating the function and regulation of neurogenesis, there remain many open questions surrounding the complexity of this phenomenon. This stems partially from the fact that neurogenesis is a multistage process that involves proliferation, differentiation, migration, survival, and eventual integration of new cells into the existing hippocampal circuitry, each of which can be independently influenced. The function of adult neurogenesis in the hippocampus is related to stress regulation, behavioral efficacy of antidepressants, long-term spatial memory, forgetting, and pattern separation. Steroid hormones influence the regulation of hippocampal neurogenesis, stress regulation, and cognition and differently in males and females. In this chapter, we will briefly tap into the complex network of steroid hormone modulation of neurogenesis in the hippocampus with specific emphasis on stress, testosterone, and estrogen. We examine the possible role of neurogenesis in the etiology of depression and influencing treatment by examining the influence of both pharmacological (selective serotonin reuptake inhibitors, tricyclic antidepressants) treatments and non-pharmacological (exercise) remedies.
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Affiliation(s)
- Ana Gheorghe
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.,Graduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada
| | - Wansu Qiu
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.,Graduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada
| | - Liisa A M Galea
- Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. .,Graduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada. .,Department of Psychology, University of British Columbia, Vancouver, BC, Canada.
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38
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Li F, Geng X, Khan H, Pendy JT, Peng C, Li X, Rafols JA, Ding Y. Exacerbation of Brain Injury by Post-Stroke Exercise Is Contingent Upon Exercise Initiation Timing. Front Cell Neurosci 2017; 11:311. [PMID: 29051728 PMCID: PMC5633611 DOI: 10.3389/fncel.2017.00311] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Accepted: 09/19/2017] [Indexed: 12/19/2022] Open
Abstract
Accumulating evidence has demonstrated that post-stroke physical rehabilitation may reduce morbidity. The effectiveness of post-stroke exercise, however, appears to be contingent upon exercise initiation. This study assessed the hypothesis that very early exercise exacerbates brain injury, induces reactive oxygen species (ROS) generation, and promotes energy failure. A total of 230 adult male Sprague-Dawley rats were subjected to middle cerebral artery (MCA) occlusion for 2 h, and randomized into eight groups, including two sham injury control groups, three non-exercise and three exercise groups. Exercise was initiated after 6 h, 24 h and 3 days of reperfusion. Twenty-four hours after completion of exercise (and at corresponding time points in non-exercise controls), infarct volumes and apoptotic cell death were examined. Early brain oxidative metabolism was quantified by examining ROS, ATP and NADH levels 0.5 h after completion of exercise. Furthermore, protein expressions of angiogenic growth factors were measured in order to determine whether post-stroke angiogenesis played a role in rehabilitation. As expected, ischemic stroke resulted in brain infarction, apoptotic cell death and ROS generation, and diminished NADH and ATP production. Infarct volumes and apoptotic cell death were enhanced (p < 0.05) by exercise that was initiated after 6 h of reperfusion, but decreased by late exercise (24 h, 3 days). This exacerbated brain injury at 6 h was associated with increased ROS levels (p < 0.05), and decreased (p < 0.05) NADH and ATP levels. In conclusion, very early exercise aggravated brain damage, and early exercise-induced energy failure with ROS generation may underlie the exacerbation of brain injury. These results shed light on the manner in which exercise initiation timing may affect post-stroke rehabilitation.
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Affiliation(s)
- Fengwu Li
- Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China
| | - Xiaokun Geng
- Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China.,Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - Hajra Khan
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - John T Pendy
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - Changya Peng
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - Xiaorong Li
- Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China
| | - Jose A Rafols
- Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, United States
| | - Yuchuan Ding
- Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China.,Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
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39
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Stevenson ME, Behnke VK, Swain RA. Exercise pattern and distance differentially affect hippocampal and cerebellar expression of FLK-1 and FLT-1 receptors in astrocytes and blood vessels. Behav Brain Res 2017; 337:8-16. [PMID: 28958753 DOI: 10.1016/j.bbr.2017.09.037] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 09/19/2017] [Accepted: 09/23/2017] [Indexed: 12/17/2022]
Abstract
Aerobic exercise benefits the body and brain. In the brain, benefits include neuroprotection and improved cognition. These exercise-induced changes are attributed in part to angiogenesis: the growth of new capillaries from preexisting vessels. One critical factor involved in the regulation of angiogenesis is VEGF and its receptors Flk-1 and Flt-1. Although exercise is generally found to be beneficial, there are wide variations in exercise regimens across experiments. This study standardized some of these variations. Rats were assigned to a voluntary or a forced wheel running exercise condition. Within each condition, animals ran for either a long (1000m) or short distance (500m) for up to 24h. Additionally, one voluntary group had unrestricted access to the wheels for the full 24h. Exercising animals were then compared to inactive controls, based on unbiased stereological quantification of Flk-1 and Flt-1 immunohistochemical labeling in the hippocampus and cerebellum. Findings indicated that voluntary exercise, but not forced exercise, could significantly increase Flk-1 and Flt-1 expression in the hippocampus. Interestingly, Flk-1 expression was elevated in astrocytes and Flt-1 in vessels. In the cerebellum long distance forced exercise resulted in the least Flk-1 expression compared to other conditions, and Flt-1 expression in exercising animals either did not change or was suppressed relative to inactive controls.
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Affiliation(s)
- Morgan E Stevenson
- Department of Psychology, University of Wisconsin Milwaukee, Milwaukee, WI, USA
| | - Vienna K Behnke
- Department of Psychology, University of Wisconsin Milwaukee, Milwaukee, WI, USA
| | - Rodney A Swain
- Department of Psychology, University of Wisconsin Milwaukee, Milwaukee, WI, USA.
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40
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The Effects of Early Exercise on Motor, Sense, and Memory Recovery in Rats With Stroke. Am J Phys Med Rehabil 2017; 96:e36-e43. [PMID: 27977432 DOI: 10.1097/phm.0000000000000670] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Exercise is an effective, inexpensive, home-based, and accessible intervention strategy for stroke treatment, and early exercise after stroke has attracted a great deal of attention in recent years. However, the effects of early exercise on comprehensive functional recovery remain poorly understood. The present study investigated the effect of early exercise on motor, sense, balance, and spatial memory recovery. DESIGN Adult Sprague-Dawley rats were subjected to unilateral middle cerebral artery occlusion (MCAO) and were randomly divided into early exercise group (EE), non-exercise group (NE), and sham group. EE group received 2 weeks of exercise training initiated at 24 hours after operation. The recovery of motor, sense, and balance function was evaluated every 3 days after MCAO. Spatial memory recovery was detected from 21 to 25 days after MCAO. RESULTS The results showed that early exercise significantly promoted the motor and spatial memory recovery with statistical differences. The rats in EE group have a better recovery in sense and balance function, but there is no statistically significant difference about these results. CONCLUSION Our results showed that early moderate exercise can significantly promote motor and spatial memory recovery, but not the sense and balance functions.
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41
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Venezia AC, Quinlan E, Roth SM. A single bout of exercise increases hippocampal Bdnf: influence of chronic exercise and noradrenaline. GENES BRAIN AND BEHAVIOR 2017; 16:800-811. [PMID: 28556463 DOI: 10.1111/gbb.12394] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 05/18/2017] [Accepted: 05/23/2017] [Indexed: 11/28/2022]
Abstract
Research in human subjects suggests that acute exercise can improve memory performance, but the qualities of the exercise necessary to promote improved memory, and the signaling pathways that mediate these effects are unknown. Brain-derived neurotrophic factor (Bdnf), noradrenergic signaling, and post-translational modifications to AMPA receptors have all been implicated in the enhancement of memory following emotional or physical arousal; however, it is not known if a single bout of exercise is sufficient to engage these pathways. Here we use a rodent model to investigate the effects of acute and chronic exercise on hippocampal transcript-specific Bdnf expression and phosphorylation of the GluR1 subunit of the AMPA-type glutamate receptor. A single bout of treadmill exercise was insufficient to mimic the increased expression of GluR1 protein and phosphorylation at Ser845 observed following 1 month of voluntary wheel running. However, acute exercise was sufficient to increase Bdnf transcript IV messenger RNA (mRNA) expression in sedentary subjects, but not subjects housed for 1 month with a running wheel. High-intensity acute exercise increased total Bdnf mRNA in sedentary mice, but not above levels observed following chronic access to the running wheel. Although depletion of central noradrenergic signaling with DSP-4 reduced Bdnf IV mRNA, the effect of acute exercise on Bdnf mRNA persisted. Our characterization of the effects of acute exercise on Bdnf expression and persistence in the absence of noradrenergic modulation may inform strategies to employ physical activity to combat cognitive aging and mental health disorders.
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Affiliation(s)
- A C Venezia
- Department of Exercise Science and Sport, The University of Scranton, Scranton, PA, USA.,Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD, USA.,Neuroscience and Cognitive Science Program, University of Maryland, College Park, MD, USA
| | - E Quinlan
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, MD, USA.,Department of Biology, University of Maryland, College Park, MD, USA
| | - S M Roth
- Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD, USA.,Neuroscience and Cognitive Science Program, University of Maryland, College Park, MD, USA
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42
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Diederich K, Bastl A, Wersching H, Teuber A, Strecker JK, Schmidt A, Minnerup J, Schäbitz WR. Effects of Different Exercise Strategies and Intensities on Memory Performance and Neurogenesis. Front Behav Neurosci 2017; 11:47. [PMID: 28360847 PMCID: PMC5352691 DOI: 10.3389/fnbeh.2017.00047] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 02/28/2017] [Indexed: 12/14/2022] Open
Abstract
It is well established that physical exercise affects both hippocampal neurogenesis and memory functions. Until now, distinctive effects of controlled and voluntary training (VT) on behavior and neurogenesis as well as interactions between exercise intensity, neurogenesis and memory performance are still elusive. The present study tested the impact of moderate controlled and VT on memory formation and hippocampal neurogenesis and evaluated interactions between exercise performance, learning efficiency and proliferation of progenitor cells in the hippocampus. Our data show that both controlled and VT augmented spatial learning and promoted hippocampal neurogenesis. Regression analysis revealed a significant linear increase of the amount of new hippocampal neurons with increased exercise intensity. Regression analysis of exercise performance on retention memory performance revealed a quadratic, inverted u-shaped relationship between exercise performance and retention of spatial memory. No association was found between the amount of newborn neurons and memory performance. Our results demonstrate that controlled training (CT), if performed with an appropriate combination of speed and duration, improves memory performance and neurogenesis. Voluntary exercise elevates neurogenesis dose dependently to high levels. Best cognitive improvement was achieved with moderate exercise performance.
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Affiliation(s)
- Kai Diederich
- Department of Neurology, University of Münster Münster, Germany
| | - Anna Bastl
- Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster Münster, Germany
| | - Heike Wersching
- Institute of Epidemiology and Social Medicine, University of Münster Münster, Germany
| | - Anja Teuber
- Institute of Epidemiology and Social Medicine, University of Münster Münster, Germany
| | | | - Antje Schmidt
- Department of Neurology, University of Münster Münster, Germany
| | - Jens Minnerup
- Department of Neurology, University of Münster Münster, Germany
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Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation. THE JOURNAL OF PAIN 2017; 18:687-701. [PMID: 28185925 DOI: 10.1016/j.jpain.2017.01.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 01/13/2017] [Accepted: 01/17/2017] [Indexed: 11/23/2022]
Abstract
Aerobic exercise improves outcomes in a variety of chronic health conditions, yet the support for exercise-induced effects on chronic pain in humans is mixed. Although many rodent studies have examined the effects of exercise on persistent hypersensitivity, the most used forced exercise paradigms that are known to be highly stressful. Because stress can also produce analgesic effects, we studied how voluntary exercise, known to reduce stress in healthy subjects, alters hypersensitivity, stress, and swelling in a rat model of persistent hind paw inflammation. Our data indicate that voluntary exercise rapidly and effectively reduces hypersensitivity as well as stress-related outcomes without altering swelling. Moreover, the level of exercise is unrelated to the analgesic and stress-reducing effects, suggesting that even modest amounts of exercise may impart significant benefit in persistent inflammatory pain states. PERSPECTIVE Modest levels of voluntary exercise reduce pain- and stress-related outcomes in a rat model of persistent inflammatory pain, independently of the amount of exercise. As such, consistent, self-regulated activity levels may be more relevant to health improvement in persistent pain states than standardized exercise goals.
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Cobianchi S, Arbat-Plana A, López-Álvarez VM, Navarro X. Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors. Curr Neuropharmacol 2017; 15:495-518. [PMID: 27026050 PMCID: PMC5543672 DOI: 10.2174/1570159x14666160330105132] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Revised: 02/19/2016] [Accepted: 03/03/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Shared connections between physical activity and neuroprotection have been studied for decades, but the mechanisms underlying this effect of specific exercise were only recently brought to light. Several evidences suggest that physical activity may be a reasonable and beneficial method to improve functional recovery in both peripheral and central nerve injuries and to delay functional decay in neurodegenerative diseases. In addition to improving cardiac and immune functions, physical activity may represent a multifunctional approach not only to improve cardiocirculatory and immune functions, but potentially modulating trophic factors signaling and, in turn, neuronal function and structure at times that may be critical for neurodegeneration and regeneration. METHODS Research content related to the effects of physical activity and specific exercise programs in normal and injured nervous system have been reviewed. RESULTS Sustained exercise, particularly if applied at moderate intensity and early after injury, exerts anti-inflammatory and pro-regenerative effects, and may boost cognitive and motor functions in aging and neurological disorders. However, newest studies show that exercise modalities can differently affect the production and function of brain-derived neurotrophic factor and other neurotrophins involved in the generation of neuropathic conditions. These findings suggest the possibility that new exercise strategies can be directed to nerve injuries with therapeutical benefits. CONCLUSION Considering the growing burden of illness worldwide, understanding of how modulation of neurotrophic factors contributes to exercise-induced neuroprotection and regeneration after peripheral nerve and spinal cord injuries is a relevant topic for research, and represents the beginning of a new non-pharmacological therapeutic approach for better rehabilitation of neural disorders.
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Affiliation(s)
- Stefano Cobianchi
- Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autonoma de Barcelona, Bellaterra, Spain
- Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain
| | - Ariadna Arbat-Plana
- Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autonoma de Barcelona, Bellaterra, Spain
- Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain
| | - Víctor M. López-Álvarez
- Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autonoma de Barcelona, Bellaterra, Spain
- Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain
| | - Xavier Navarro
- Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autonoma de Barcelona, Bellaterra, Spain
- Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain
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45
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Chen CC, Yang CL, Chang CP. An Innovative Running Wheel-based Mechanism for Improved Rat Training Performance. J Vis Exp 2016. [PMID: 27684092 DOI: 10.3791/54354] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
This study presents an animal mobility system, equipped with a positioning running wheel (PRW), as a way to quantify the efficacy of an exercise activity for reducing the severity of the effects of the stroke in rats. This system provides more effective animal exercise training than commercially available systems such as treadmills and motorized running wheels (MRWs). In contrast to an MRW that can only achieve speeds below 20 m/min, rats are permitted to run at a stable speed of 30 m/min on a more spacious and high-density rubber running track supported by a 15 cm wide acrylic wheel with a diameter of 55 cm in this work. Using a predefined adaptive acceleration curve, the system not only reduces the operator error but also trains the rats to run persistently until a specified intensity is reached. As a way to evaluate the exercise effectiveness, real-time position of a rat is detected by four pairs of infrared sensors deployed on the running wheel. Once an adaptive acceleration curve is initiated using a microcontroller, the data obtained by the infrared sensors are automatically recorded and analyzed in a computer. For comparison purposes, 3 week training is conducted on rats using a treadmill, an MRW and a PRW. After surgically inducing middle cerebral artery occlusion (MCAo), modified neurological severity scores (mNSS) and an inclined plane test were conducted to assess the neurological damages to the rats. PRW is experimentally validated as the most effective among such animal mobility systems. Furthermore, an exercise effectiveness measure, based on rat position analysis, showed that there is a high negative correlation between the effective exercise and the infarct volume, and can be employed to quantify a rat training in any type of brain damage reduction experiments.
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Affiliation(s)
- Chi-Chun Chen
- Department of Electronic Engineering, National Chin-Yi University of Technology;
| | - Chin-Lung Yang
- Department of Electrical Engineering, National Cheng Kung University
| | - Ching-Ping Chang
- Department of Biotechnology, Southern Taiwan University of Science and Technology; Department of Medical Research, Chi Mei Medical Center
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46
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Gram MG, Wogensen E, Moseholm K, Mogensen J, Malá H. Exercise-induced improvement in cognitive performance after fimbria-fornix transection depends on the timing of exercise administration. Brain Res Bull 2016; 125:117-26. [DOI: 10.1016/j.brainresbull.2016.06.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 06/15/2016] [Accepted: 06/21/2016] [Indexed: 01/29/2023]
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Constans A, Pin-Barre C, Temprado JJ, Decherchi P, Laurin J. Influence of Aerobic Training and Combinations of Interventions on Cognition and Neuroplasticity after Stroke. Front Aging Neurosci 2016; 8:164. [PMID: 27445801 PMCID: PMC4928497 DOI: 10.3389/fnagi.2016.00164] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 06/21/2016] [Indexed: 12/17/2022] Open
Abstract
Stroke often aggravated age-related cognitive impairments that strongly affect several aspects of quality of life. However, few studies are, to date, focused on rehabilitation strategies that could improve cognition. Among possible interventions, aerobic training is well known to enhance cardiovascular and motor functions but may also induce beneficial effects on cognitive functions. To assess the effectiveness of aerobic training on cognition, it seems necessary to know whether training promotes the neuroplasticity in brain areas involved in cognitive functions. In the present review, we first explore in both human and animal how aerobic training could improve cognition after stroke by highlighting the neuroplasticity mechanisms. Then, we address the potential effect of combinations between aerobic training with other interventions, including resistance exercises and pharmacological treatments. In addition, we postulate that classic recommendations for aerobic training need to be reconsidered to target both cognition and motor recovery because the current guidelines are only focused on cardiovascular and motor recovery. Finally, methodological limitations of training programs and cognitive function assessment are also developed in this review to clarify their effectiveness in stroke patients.
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Affiliation(s)
| | - Caroline Pin-Barre
- Aix-Marseille Université, CNRS, ISM, UMR 7287Marseille, France; Université Nice Sophia Antipolis, LAMHESS, UPRES EA 6309Nice, France
| | | | | | - Jérôme Laurin
- Aix-Marseille Université, CNRS, ISM, UMR 7287 Marseille, France
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48
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Ebada ME, Kendall DA, Pardon MC. Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice. Behav Brain Res 2016; 311:228-238. [PMID: 27233827 DOI: 10.1016/j.bbr.2016.05.051] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Revised: 04/07/2016] [Accepted: 05/23/2016] [Indexed: 12/13/2022]
Abstract
Physical exercise can improve cognition but whether this is related to motivation levels is unknown. Voluntary wheel running is a rewarding activity proposed as a model of motivation to exercise. To question the potential effects of exercise motivation on subsequent behaviour, we used a pharmacological approach targeting some reward mechanisms. The stress hormone corticosterone has rewarding effects mediated by activation of low affinity glucocorticoid receptors (GR). To investigate whether corticosterone synthesis motivates exercise via activation of GRs and subsequently, impacts on behaviour, we treated C57BL/6J mice acutely with the inhibitor of corticosterone synthesis metyrapone (35mg/kg) or repeatedly with the GR antagonist mifepristone (30mg/kg) prior to 1-h running wheel sessions. To investigate whether reducing motivation to exercise impacts on behaviour, we antagonised running-induced dopamine D2/D3 receptors activation with sulpiride (25 or 50mg/kg) and assessed locomotor, anxiety-related and memory performance after 20 running sessions over 4 weeks. We found that corticosterone synthesis contributes to running levels, but the maintenance of running behaviour was not mediated by activation of GRs. Intermittent exercise was not associated with changes in behavioural or cognitive performance. The persistent reduction in exercise levels triggered by sulpiride also had limited impact on behavioural performance, although the level of performance for some behaviours was related to the level of exercise. Altogether, these findings indicate that corticosterone and dopamine D2/D3 receptor activation contribute to the motivation for wheel running, but suggest that motivation for exercise is not a sufficient factor to alter behaviour in healthy mice.
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Affiliation(s)
- Mohamed Elsaed Ebada
- University of Nottingham Medical School, School of Life Sciences, Neuroscience Group, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom
| | - David A Kendall
- University of Nottingham Medical School, School of Life Sciences, Neuroscience Group, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom
| | - Marie-Christine Pardon
- University of Nottingham Medical School, School of Life Sciences, Neuroscience Group, Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
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49
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The effects of hormones and physical exercise on hippocampal structural plasticity. Front Neuroendocrinol 2016; 41:23-43. [PMID: 26989000 DOI: 10.1016/j.yfrne.2016.03.001] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 03/02/2016] [Accepted: 03/08/2016] [Indexed: 01/22/2023]
Abstract
The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration.
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50
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Otsuka S, Sakakima H, Sumizono M, Takada S, Terashi T, Yoshida Y. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats. Behav Brain Res 2016; 303:9-18. [DOI: 10.1016/j.bbr.2016.01.049] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 01/18/2016] [Accepted: 01/20/2016] [Indexed: 01/07/2023]
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