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Silva AF, Clemente FM, Roriz MS, Azevedo JA, Jovanovic O, Adamovic M, Bozic A, Silva R. The Effect of Aerobic or Strength Training in Elderly with Cognitive Decline: The Fit4Alz Project. J Sports Sci Med 2025; 24:172-186. [PMID: 40046223 PMCID: PMC11877294 DOI: 10.52082/jssm.2025.172] [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: 12/20/2024] [Accepted: 02/02/2025] [Indexed: 05/13/2025]
Abstract
This study aimed to examine the effects of aerobic and strength training methodologies, either combined with or without cognitive training, on mitigating cognitive decline. A total of 154 subjects were recruited (72.8 ± 6.1 years, 69% females) and were divided into four groups: i) strength plus cognitive training (STCT, n = 56); ii) strength training (ST, n = 23); iii) aerobic training (AT, n = 41); and iv) aerobic plus cognitive training (ATCT, n = 34). Subjects were previously cognitively assessed and showed cognitive decline (less than 26 points on the Montreal Cognitive Assessment, MoCA). For 12 weeks, all groups performed 3 times a week, for 60 minutes, a training program corresponding to their attributed group. The MoCA test and the Senior Fitness test were applied at the beginning and the end of the intervention. A repeated-measures ANCOVA revealed significant time-by-group interactions for physical performance measures, including the 2-minute step-in-place (p = 0.026), arm curl (p < 0.001), chair sit-and-reach (p < 0.001), back-scratch (p < 0.001), 8-foot up-and-go (p < 0.001), and 6-minute walk tests (p < 0.001). However, no significant improvements were observed for cognitive function (MoCA, p = 0.242) or lower body strength (chair stand, p = 0.411). The AT group showed greater improvements in upper body strength compared to STCT and ST (p < 0.001; d = 0.698; p = 0.004; d = 0.598), while STCT significantly improved flexibility compared to ATCT (p < 0.001; d = 1.049). ATCT had the greatest improvements in aerobic endurance compared to STCT and ST (p = 0.004; d = 0.133; p < 0.001; d = 0.350). It was demonstrated that aerobic and strength training significantly improved overall physical performance in elderly individuals. However, no significant effects were observed on cognitive performance. Although these findings suggest that both aerobic and strength exercise, with or without cognitive training, improve overall physical fitness, further research is needed to determine its impact on cognitive performance.
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Affiliation(s)
- Ana Filipa Silva
- Escola Superior Desporto e Lazer, Instituto Politécnico de Viana do Castelo, Rua Escola Industrial e Comercial de Nun'Álvares, 4900-347Viana do Castelo, Portugal
- Sport Physical Activity and Health Research & Innovation Center (SPRINT), 4900-347 Viana do Castelo, Portugal
| | - Filipe Manuel Clemente
- Escola Superior Desporto e Lazer, Instituto Politécnico de Viana do Castelo, Rua Escola Industrial e Comercial de Nun'Álvares, 4900-347Viana do Castelo, Portugal
- Sport Physical Activity and Health Research & Innovation Center (SPRINT), 4900-347 Viana do Castelo, Portugal
- Gdansk University of Physical Education and Sport, 80-336 Gdańsk, Poland
| | - Mafalda Sofia Roriz
- Câmara Municipal da Maia, Praça do Doutor José Vieira de Carvalho, 4474-006 Maia, Portugal
- Universidade da Maia - UMAIA, Avenida Carlos de Oliveira Campos, Castêlo da Maia, 4475-690 Maia, Portugal
| | - José Alberto Azevedo
- Câmara Municipal da Maia, Praça do Doutor José Vieira de Carvalho, 4474-006 Maia, Portugal
| | - Olivera Jovanovic
- Association Sport for all Vojvodina (ASFAV), Masarikova 25, 21000 Novi Sad, Serbia
| | - Marko Adamovic
- Association Sport for all Vojvodina (ASFAV), Masarikova 25, 21000 Novi Sad, Serbia
| | - Aleksandar Bozic
- Association Sport for all Vojvodina (ASFAV), Masarikova 25, 21000 Novi Sad, Serbia
| | - Rui Silva
- Escola Superior Desporto e Lazer, Instituto Politécnico de Viana do Castelo, Rua Escola Industrial e Comercial de Nun'Álvares, 4900-347Viana do Castelo, Portugal
- Sport Physical Activity and Health Research & Innovation Center (SPRINT), 4900-347 Viana do Castelo, Portugal
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Shearon J, Jackson J, Head D. Role of Cardiovascular Risk in Associations of Brain-Derived Neurotrophic Factor with Longitudinal Brain and Cognitive Trajectories in Older Adults. Exp Aging Res 2024:1-21. [PMID: 39514806 DOI: 10.1080/0361073x.2024.2423593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Higher levels of brain-derived neurotrophic factor (BDNF) have been associated with better neurocognitive outcomes. BDNF is present in cardiovascular tissue, and some evidence suggests it may benefit cardiovascular function. The current study assessed whether there is a mediating and/or moderating role of cardiovascular health in the relationship between BDNF and brain and cognitive outcomes. METHOD We examined longitudinal data from 397 older adults (aged 54-89;164 females, 233 males) enrolled in the Alzheimer's Disease Neuroimaging Initiative with available plasma BDNF, medical, neuroimaging, and cognitive assessments. We used path analysis and linear regression to estimate the mediating and moderating roles of two measures of cardiovascular health, the Framingham Risk Score (FRS) and pulse pressure, in the relationships between BDNF and longitudinal changes in brain structure (white matter hyperintensity volume, hippocampal volume, and primary visual cortex volume) and cognitive function (executive function, episodic memory, and language). RESULTS There was no significant association of plasma BDNF with FRS or pulse pressure (ps > 0.31), precluding mediation. There were no robust associations between BDNF and longitudinal change in any brain structural or cognitive measures (ps > .12). Higher FRS was significantly associated with greater increases in WMH volume (ps < .01). FRS and pulse pressure were not associated with any other brain structural or cognitive outcomes (ps > .07). CONCLUSION These results suggest that cardiovascular health may not play an important role in the influence of BDNF on neurocognitive health in older adults.
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Affiliation(s)
- Jennifer Shearon
- Department of Psychological and Brain Sciences, Washington University, St. Louis, Missouri, USA
| | - Joshua Jackson
- Department of Psychological and Brain Sciences, Washington University, St. Louis, Missouri, USA
| | - Denise Head
- Department of Psychological and Brain Sciences, Washington University, St. Louis, Missouri, USA
- Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA
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Keegan AP, Stough C, Paris D, Luis CA, Abdullah L, Ait-Ghezala G, Chaykin J, Crawford F, Mullan M. Baseline serum brain-derived neurotrophic factor association with future cognition in community-dwelling older adults undergoing annual memory screening. Neurol Res 2024; 46:253-260. [PMID: 38095353 DOI: 10.1080/01616412.2023.2294581] [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: 04/16/2023] [Accepted: 12/09/2023] [Indexed: 01/24/2024]
Abstract
OBJECTIVES It has been shown that peripheral measures of brain-derived neurotrophic factor (BNDF), an important neurotrophin instrumental to the biology of learning, may contribute to predicting cognitive decline. However, the two primary forms of BDNF, mature (mBDNF) and pro (proBDNF), and how they contribute to cognition longitudinally has not been well studied. METHODS Eighty-two older adults (average age 72.2 ± 6.4 years) provided blood samples at two time points separated on average by 4.2 years while participating in an annual memory screening that included the MoCA (Montreal Cognitive Assessment) and GDS (Geriatric Depression Scale). Both mBDNF and proBDNF from serum were quantified at each time point. Whole blood samples were genotyped for APOE and BDNF Val66Met. RESULTS Using logistic regression analysis controlling for age, sex, baseline MoCA score, APOE, and BDNF, higher baseline mBDNF was associated with subjects whose screening score was near maximum or maximum (as defined by MoCA score of 29 or 30) at the second collection visit. APOE was a significant contributing factor; however, BDNF Val66Met was not. Using a similar logistic regression analysis, baseline proBDNF was not found to be associated with future cognition. DISCUSSION This study further supports that mBDNF measured in the serum of older adults may reflect a protective role while proBDNF requires further investigation.
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Affiliation(s)
| | - Con Stough
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, Australia
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Ružić M, Rajić N, Nikolašević Ž, Spasić A, Pete M, Ignjatović VB. Is there a connection between neurocognitive profile in treatment naïve non-cirrhotic HCV patients and level of systemic inflammation? J Neurovirol 2023; 29:723-730. [PMID: 37948037 DOI: 10.1007/s13365-023-01184-6] [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: 01/17/2023] [Revised: 10/18/2023] [Accepted: 10/26/2023] [Indexed: 11/12/2023]
Abstract
Hepatitis C virus (HCV) infection is a progressive, systemic disease which leads to the development of end-stage liver disease. In 70% of patients, HCV infection is followed by the development of extrahepatic manifestations (EHM). A common EHM is HCV associated neurocognitive disorder (HCV-AND), characterized by neuropsychological changes in attention, working memory, psychomotor speed, executive function, verbal learning, and recall. The aim of this study is to examine the correlation between the neurocognitive profile and routine, available laboratory parameters of inflammation, liver function tests, grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia in treatment naïve non-cirrhotic HCV patients. This is a single-center exploratory study in which we examined 38 HCV + treatment naïve patients. The complete blood count and hematological parameters of systemic inflammation, liver function tests, biopsy confirmed grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia caused by chronic HCV infection were observed. In the study, we used a battery of neuropsychological tests assessing multiple cognitive domains: executive functions, verbal fluency, delayed memory, working memory and learning, and one measure for visuo-constructive performance. Before the Bonferroni correction for multiple comparisons, the results show significant correlations between the scores in the neurocognitive variables and the single measures of inflammation, liver function parameters, and mixed cryoglobulinemia. It has not found a statistically significant correlation between systemic inflammation and neurocognitive variables. After the Bonferroni adjustment, no correlations remained significant. Certainly, the obtained results can be a recommendation for additional validation through future research.
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Affiliation(s)
- Maja Ružić
- Faculty of Medicine, University of Novi Sad, Clinic for Infectious Diseases, University Clinical Centre of Vojvodina, Novi Sad, Serbia.
| | - Natalija Rajić
- Faculty of Medicine, University of Novi Sad, Clinic for Infectious Diseases, University Clinical Centre of Vojvodina, Novi Sad, Serbia
| | - Željka Nikolašević
- Faculty of Medicine, Department of Psychology, University of Novi Sad, Novi Sad, Serbia
| | - Aleksandar Spasić
- Faculty of Medicine, University of Novi Sad, Center for Radiology, University Clinical Centre of Vojvodina, Novi Sad, Serbia
| | - Maria Pete
- Faculty of Medicine, University of Novi Sad, Clinic for Infectious Diseases, University Clinical Centre of Vojvodina, Novi Sad, Serbia
| | - Vojislava Bugarski Ignjatović
- Faculty of Medicine, Department of Psychology, University of Novi Sad, Novi Sad, Serbia
- Faculty of Medicine, University of Novi Sad, Neurology Clinic, University Clinical Centre of Vojvodina, Novi Sad, Serbia
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Fong TKH, Cheung T, Ngan STJ, Tong K, Lui WYV, Chan WC, Wong CSM, Cheng CPW. Transcranial pulse stimulation in the treatment of mild neurocognitive disorders. Ann Clin Transl Neurol 2023; 10:1885-1890. [PMID: 37607114 PMCID: PMC10578878 DOI: 10.1002/acn3.51882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/03/2023] [Accepted: 08/04/2023] [Indexed: 08/24/2023] Open
Abstract
OBJECTIVE There are limited effectiveness and potential side effects of existing pharmacological approach in treating mild neurocognitive disorder (NCD). Transcranial pulse stimulation (TPS) applies repetitive single high-pressure ultrashort shockwave pulses to stimulate the brain, which has been shown to effectively improve cognition in major NCD. However, the effectiveness of TPS in mild NCD patients remained unknown. This study aims to assess the effectiveness and tolerability of TPS with neuro-navigation in old-age adults with mild NCD by both clinical and biochemical assessments. METHODS An open-label study recruited older adults with mild NCD to receive neuro-navigated TPS intervention for two weeks with three sessions per week. Assessments included detailed cognitive assessments, APOE genotype, and brain-derived neurotrophic factor (BDNF). RESULTS Nineteen participants (12 females and 7 males) completed the whole TPS interventions with no serious adverse effects reported. Repeated measures ANOVA showed statistically significant effects of time on HK-MoCA (F (3, 54) = 4.99, P = 0.004), 30-sec interval of Verbal Fluency Test (F (3, 54) = 2.94, P = 0.041), Stroop interference (F (3, 54) = 3.46, P = 0.023), and Chinese IADL (F (3, 54) = 2.78, P = 0.050) after receiving the intervention. Bonferroni post hoc comparisons on HK-MoCA showed a significant improvement after intervention. There was no significant change in serum BDNF level. INTERPRETATION TPS has brought significant improvement in cognition of elderly with mild NCD. It has a great potential to delay the deterioration of cognition in older adults. The long-term effect of TPS in cognition would benefit from further large-scale, randomized, sham-controlled trials.
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Affiliation(s)
| | - Teris Cheung
- School of NursingThe Hong Kong Polytechnic UniversityHong KongChina
| | | | - Kelvin Tong
- Department of PsychiatryThe University of Hong KongHong KongChina
| | | | - Wai Chi Chan
- Department of PsychiatryThe University of Hong KongHong KongChina
| | - Corine Sau Man Wong
- Division of Community Medicine and Public Health PracticeThe University of Hong KongHong KongChina
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Nikolac Perkovic M, Borovecki F, Filipcic I, Vuic B, Milos T, Nedic Erjavec G, Konjevod M, Tudor L, Mimica N, Uzun S, Kozumplik O, Svob Strac D, Pivac N. Relationship between Brain-Derived Neurotrophic Factor and Cognitive Decline in Patients with Mild Cognitive Impairment and Dementia. Biomolecules 2023; 13:biom13030570. [PMID: 36979505 PMCID: PMC10046678 DOI: 10.3390/biom13030570] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/10/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
In the last decade, increasing evidence has emerged linking alterations in the brain-derived neurotrophic factor (BDNF) expression with the development of Alzheimer's disease (AD). Because of the important role of BDNF in cognition and its association with AD pathogenesis, the aim of this study was to evaluate the potential difference in plasma BDNF concentrations between subjects with mild cognitive impairment (MCI; N = 209) and AD patients (N = 295) and to determine the possible association between BDNF plasma levels and the degree of cognitive decline in these individuals. The results showed a significantly higher (p < 0.001) concentration of plasma BDNF in subjects with AD (1.16; 0.13-21.34) compared with individuals with MCI (0.68; 0.02-19.14). The results of the present study additionally indicated a negative correlation between cognitive functions and BDNF plasma concentrations, suggesting higher BDNF levels in subjects with more pronounced cognitive decline. The correlation analysis revealed a significant negative correlation between BDNF plasma levels and both Mini-Mental State Examination (p < 0.001) and Clock Drawing test (p < 0.001) scores. In conclusion, the results of our study point towards elevated plasma BDNF levels in AD patients compared with MCI subjects, which may be due to the body's attempt to counteract the early and middle stages of neurodegeneration.
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Affiliation(s)
- Matea Nikolac Perkovic
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
| | - Fran Borovecki
- Department of Neurology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Igor Filipcic
- Psychiatric Hospital "Sveti Ivan", 10090 Zagreb, Croatia
| | - Barbara Vuic
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
| | - Tina Milos
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
| | - Gordana Nedic Erjavec
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
| | - Marcela Konjevod
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
| | - Lucija Tudor
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
| | - Ninoslav Mimica
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapče, 10090 Zagreb, Croatia
| | - Suzana Uzun
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapče, 10090 Zagreb, Croatia
| | - Oliver Kozumplik
- Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapče, 10090 Zagreb, Croatia
| | - Dubravka Svob Strac
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
| | - Nela Pivac
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia
- University of Applied Sciences Hrvatsko Zagorje Krapina, 49000 Krapina, Croatia
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Banerjee M, Shenoy RR. Emphasizing roles of BDNF promoters and inducers in Alzheimer's disease for improving impaired cognition and memory. J Basic Clin Physiol Pharmacol 2023; 34:125-136. [PMID: 34751526 DOI: 10.1515/jbcpp-2021-0182] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 10/11/2021] [Indexed: 12/13/2022]
Abstract
Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophic factor adding to neurons' development and endurance. The amount of BDNF present in the brain determines susceptibility to various neurodegenerative diseases. In Alzheimer's disease (AD), often it is seen that low levels of BDNF are present, which primarily contributes to cognition deficit by regulating long-term potentiation (LTP) and synaptic plasticity. Molecular mechanisms underlying the synthesis, storage and release of BDNF are widely studied. New molecules are found, which contribute to the signal transduction pathway. Two important receptors of BDNF are TrkB and p75NTR. When BDNF binds to the TrkB receptor, it activates three main signalling pathways-phospholipase C, MAPK/ERK, PI3/AKT. BDNF holds an imperative part in LTP and dendritic development, which are essential for memory formation. BDNF supports synaptic integrity by influencing LTP and LTD. This action is conducted by modulating the glutamate receptors; AMPA and NMDA. This review paper discusses the aforesaid points along with inducers of BDNF. Drugs and herbals promote neuroprotection by increasing the hippocampus' BDNF level in various disease-induced animal models for neurodegeneration. Advancement in finding pertinent molecules contributing to the BDNF signalling pathway has been discussed, along with the areas that require further research and study.
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Affiliation(s)
- Madhuparna Banerjee
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi District, Karnataka, India
| | - Rekha R Shenoy
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi District, Karnataka, India
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Azoulay D, Naamad M, Frydman D, Broide E, Zimran A, Stemer G, Revel-Vilk S. Brain-Derived Neurotrophic Factor (BDNF) Is Associated with Platelet Activity and Bleeding Tendency in Patients with Gaucher Disease. Int J Mol Sci 2022; 23:13982. [PMID: 36430458 PMCID: PMC9697957 DOI: 10.3390/ijms232213982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Bleeding tendency, a prominent feature of patients with Gaucher disease (GD), is associated with abnormal platelet function. Brain-derived neurotrophic factor (BDNF) is a protein with neuroprotective potential stored in alpha granules of circulating platelets. Here we studied BDNF levels in 50 patients with type I GD (GD1) and their correlation with platelet activity and bleeding tendency. Flow cytometry was used to test unstimulated and stimulated measurement of platelet surface-activated expression of αIIbβ3 integrin, P-selectin and lysosomal-associated membrane protein (LAMP3/CD63). Serum and plasma BDNF levels were quantified using ELISA. The bleeding history was recorded by a bleeding questionnaire. Serum BDNF levels were positively correlated with platelet count and moderately correlated with unstimulated and stimulated platelet P-selectin expression. Patients with more than one bleeding manifestation were shown to have lower serum BDNF levels, albeit similar platelet count. Plasma BDNF levels were significantly elevated in splenectomized patients and showed a moderate positive correlation with stimulated platelet CD63 expression. These observations demonstrate the first association between BDNF levels in the peripheral blood with platelet dysfunction and increased bleeding manifestation. The role of measuring serum BDNF for assessing platelet alpha degranulation defects and bleeding risk in patients with GD and the general population needs further study.
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Affiliation(s)
- David Azoulay
- Hematology Unit and Laboratories, Galilee Medical Center, Nahariya 22100, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Mira Naamad
- Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
| | - Dafna Frydman
- Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
| | - Ellen Broide
- Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
| | - Ari Zimran
- Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel
| | - Galia Stemer
- Hematology Unit and Laboratories, Galilee Medical Center, Nahariya 22100, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel
| | - Shoshana Revel-Vilk
- Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel
- Pediatric Hematology/Oncology Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
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Travica N, Aslam H, O'Neil A, Lane MM, Berk M, Gamage E, Walder K, Liu ZS, Segasby T, Marx W. Brain derived neurotrophic factor in perioperative neurocognitive disorders: Current evidence and future directions. Neurobiol Learn Mem 2022; 193:107656. [DOI: 10.1016/j.nlm.2022.107656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/25/2022] [Accepted: 06/28/2022] [Indexed: 10/17/2022]
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Kim SH, Kim KH, Hyun JW, Kim JH, Seo SS, Kim HJ, Park SY, Lim MC. Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers. Front Oncol 2022; 12:942960. [PMID: 36059704 PMCID: PMC9428708 DOI: 10.3389/fonc.2022.942960] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/27/2022] [Indexed: 11/20/2022] Open
Abstract
Objective We aimed to evaluate the potential of serum neurofilament light chain (sNfL) and serum brain-derived neurotrophic factor (sBDNF) as reliable biomarkers for paclitaxel-induced peripheral neuropathy (PIPN). Methods Forty-eight patients with gynecologic cancer scheduled to undergo six cycles of paclitaxel-based chemotherapy at the National Cancer Center of Korea between September 2020 and January 2022 were prospectively assessed during and after chemotherapy. Results At the end of the chemotherapy, 12 (25%) patients were classified as having grade 3 PIPN according to the National Cancer Institute-Common Toxicity Criteria. The sNfL levels increased during paclitaxel treatment in all patients. After two, four, and six cycles, patients with grade 3 PIPN exhibited higher mean sNfL levels than those in the 0-2 grade range (p = 0.004, p = 001, and p < 0.001, respectively). For sNfL levels ≥ 124 pg/mL, after two cycles of chemotherapy, the sensitivity and specificity for predicting grade 3 PIPN at the end of treatment were 80% and 79%, respectively. Over the course of paclitaxel-based treatment, sBDNF levels continued to decrease regardless of the severity of PIPN. At the end of treatment and six months after chemotherapy, patients with grade 3 PIPN had lower sBDNF levels than those within the 0-2 grade range (p =0.037 and 0.02, respectively), and the patients in the latter group had better clinical symptoms six months after the end of treatment. Conclusions The sNfL levels during paclitaxel-based chemotherapy reflect ongoing neuroaxonal injury and serve as reliable biomarkers of PIPN severity. The sNfL levels during early treatment with paclitaxel might be prognostic indicators for PIPN progression. Low sBDNF levels 6 months after chemotherapy might adversely affect PIPN recovery.
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Affiliation(s)
- Su-Hyun Kim
- Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea
| | - Ki Hoon Kim
- Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea
| | - Jae-Won Hyun
- Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea
| | - Ji Hyun Kim
- Center for Gynecologic Cancer, National Cancer Center, Goyang, South Korea
| | - Sang-Soo Seo
- Center for Gynecologic Cancer, National Cancer Center, Goyang, South Korea
| | - Ho Jin Kim
- Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea
| | - Sang-Yoon Park
- Center for Gynecologic Cancer, National Cancer Center, Goyang, South Korea
| | - Myong Cheol Lim
- Center for Gynecologic Cancer, National Cancer Center, Goyang, South Korea
- Center for Clinical Trial, Hospital, National Cancer Center, Goyang, South Korea
- Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, South Korea
- Rare and Pediatric Cancer Branch and Immuno-oncology Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang, South Korea
- Department of Cancer Control and Policy, National Cancer Center, Goyang, South Korea
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Hashimoto M, Matsuzaki K, Maruyama K, Sumiyoshi E, Hossain S, Wakatsuki H, Kato S, Ohno M, Tanabe Y, Kuroda Y, Yamaguchi S, Kajima K, Ohizumi Y, Shido O. Perilla frutescens seed oil combined with Anredera cordifolia leaf powder attenuates age-related cognitive decline by reducing serum triglyceride and glucose levels in healthy elderly Japanese individuals: a possible supplement for brain health. Food Funct 2022; 13:7226-7239. [PMID: 35722977 DOI: 10.1039/d2fo00723a] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
We have shown that Anredera cordifolia extract improves learning and memory in a senescence-accelerated mouse model, and that α-linolenic acid (ALA)-rich Perilla frutescens seed oil (PO) improves brain function in healthy Japanese adults and elderly individuals. Herein, we present a 12-month, randomised, double-blind, parallel-armed intervention trial examining the effects of PO supplementation alone or in combination with A. cordifolia leaf powder on brain function in healthy elderly Japanese individuals. Participants were randomly divided into two groups: the PO group received 1.47 mL PO (0.88 g ALA) daily via soft gelatine capsules, and the POAC group received 1.47 mL PO and 1.12 g A. cordifolia leaf powder (1.46 mg vitexin and 1.12 mg adenosine) daily. After 12 months of intervention, the POAC group showed generally higher cognitive index scores than the PO group. The beneficial effects of combined supplementation on cognitive function were associated with increased ALA and eicosapentaenoic acid levels in red blood cell plasma membranes, increased serum biological antioxidant potential, and decreased serum triglyceride, glucose, and N-(epsilon)-carboxymethyl-lysine (CML), an advanced glycation end-product and biochemical marker of oxidative stress levels. The effects of combined supplementation on cognitive function also showed a significant negative correlation with serum CML levels after 12 months of intervention. Our findings suggest that combined long-term supplementation with PO and A. cordifolia more effectively ameliorates age-related cognitive decline than PO alone. These findings may serve as a basis for the development of new supplements for brain health. Clinical Trial Registry, UMIN000040863.
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Affiliation(s)
- Michio Hashimoto
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
| | - Kentaro Matsuzaki
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
| | | | - Eri Sumiyoshi
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
| | - Shahdat Hossain
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, Bangladesh
| | - Harumi Wakatsuki
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
| | - Setsushi Kato
- Kato Hospital, Jinjukai Healthcare Corporation, Kawamoto, Shimane, Japan
| | - Miho Ohno
- Kato Hospital, Jinjukai Healthcare Corporation, Kawamoto, Shimane, Japan
| | - Yoko Tanabe
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
| | - Yoko Kuroda
- Department of Internal Medicine III, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan
| | | | - Koji Kajima
- Sankyo Holdings Co., Ltd, Fuji, Shizuoka, Japan
| | - Yasushi Ohizumi
- Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai, Miyagi, Japan
| | - Osamu Shido
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
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12
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BDNF and Pro-BDNF in Amyotrophic Lateral Sclerosis: A New Perspective for Biomarkers of Neurodegeneration. Brain Sci 2022; 12:brainsci12050617. [PMID: 35625004 PMCID: PMC9139087 DOI: 10.3390/brainsci12050617] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 04/28/2022] [Accepted: 05/06/2022] [Indexed: 02/01/2023] Open
Abstract
Amyotrophic Lateral Sclerosis (ALS) is characterized by the progressive degeneration of upper or lower motor neurons, leading to muscle wasting and paralysis, resulting in respiratory failure and death. The precise ALS aetiology is poorly understood, mainly due to clinical and genetic heterogeneity. Thus, the identification of reliable biomarkers of disease could be helpful in clinical practice. In this study, we investigated whether the levels of brain-derived neurotrophic factor (BDNF) and its precursor Pro-BDNF in serum and cerebrospinal fluid (CSF) may reflect the pathological changes related to ALS. We found higher BDNF and lower Pro-BDNF levels in ALS sera compared to healthy controls. BDNF/Pro-BDNF ratio turned out to be accurate in distinguishing ALS patients from controls. Then, the correlations of these markers with several ALS clinical variables were evaluated. This analysis revealed three statistically significant associations: (1) Patients carrying the C9orf72 expansion significantly differed from non-carrier patients and showed serum BDNF levels comparable to control subjects; (2) BDNF levels in CSF were significantly higher in ALS patients with faster disease progression; (3) lower serum levels of Pro-BDNF were associated with a shorter survival. Therefore, we suggest that BDNF and Pro-BDNF, alone or in combination, might be used as ALS prognostic biomarkers.
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13
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Gao L, Zhang Y, Sterling K, Song W. Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential. Transl Neurodegener 2022; 11:4. [PMID: 35090576 PMCID: PMC8796548 DOI: 10.1186/s40035-022-00279-0] [Citation(s) in RCA: 231] [Impact Index Per Article: 77.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 01/01/2022] [Indexed: 12/14/2022] Open
Abstract
Synaptic abnormalities are a cardinal feature of Alzheimer's disease (AD) that are known to arise as the disease progresses. A growing body of evidence suggests that pathological alterations to neuronal circuits and synapses may provide a mechanistic link between amyloid β (Aβ) and tau pathology and thus may serve as an obligatory relay of the cognitive impairment in AD. Brain-derived neurotrophic factors (BDNFs) play an important role in maintaining synaptic plasticity in learning and memory. Considering AD as a synaptic disorder, BDNF has attracted increasing attention as a potential diagnostic biomarker and a therapeutical molecule for AD. Although depletion of BDNF has been linked with Aβ accumulation, tau phosphorylation, neuroinflammation and neuronal apoptosis, the exact mechanisms underlying the effect of impaired BDNF signaling on AD are still unknown. Here, we present an overview of how BDNF genomic structure is connected to factors that regulate BDNF signaling. We then discuss the role of BDNF in AD and the potential of BDNF-targeting therapeutics for AD.
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Affiliation(s)
- Lina Gao
- Shandong Collaborative Innovation Center for Diagnosis, Treatment and Behavioral Interventions of Mental Disorders, Institute of Mental Health, College of Pharmacy, Jining Medical University, Jining, 272067, Shandong, China
- Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada
| | - Yun Zhang
- National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
| | - Keenan Sterling
- Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada
| | - Weihong Song
- Shandong Collaborative Innovation Center for Diagnosis, Treatment and Behavioral Interventions of Mental Disorders, Institute of Mental Health, College of Pharmacy, Jining Medical University, Jining, 272067, Shandong, China.
- Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
- National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
- Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, School of Mental Health and The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, 325001, Zhejiang, China.
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14
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Hashimoto M, Matsuzaki K, Maruyama K, Hossain S, Sumiyoshi E, Wakatsuki H, Kato S, Ohno M, Tanabe Y, Kuroda Y, Yamaguchi S, Kajima K, Ohizumi Y, Shido O. Perilla seed oil in combination with the nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: Possible supplement for brain health in the elderly. Food Funct 2022; 13:2768-2781. [DOI: 10.1039/d1fo03508h] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Perilla (Perilla frutescens) seed oil (PO), rich in α-linolenic acid (ALA), can improve cognitive function in healthy elderly Japanese people. Here, supplements containing either PO alone or PO with nobiletin-rich...
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15
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Azoulay D, Horowitz NA. Brain-derived neurotrophic factor in hematological malignancies: From detrimental to potentially beneficial. Blood Rev 2021; 51:100871. [PMID: 34344590 DOI: 10.1016/j.blre.2021.100871] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/13/2021] [Accepted: 07/21/2021] [Indexed: 12/20/2022]
Abstract
Emerging studies have highlighted brain-derived neurotrophic factor (BDNF), a neuronal growth factor abundant in the peripheral blood, and its tyrosine kinase receptor TRKB, as onco-genes and proteins that support the survival of malignant hematological cells. In contrast, other researchers reported on a favorable association between BDNF blood levels and prognosis, chemotherapy response and neurological side effects in patients with hematological malignancies. Here, we review the accumulated data regarding the expression of BDNF and its receptors in normal hematopoietic and lymphatic cells and tissue. In addition, in-vitro experiments, animal models and human sample studies that investigated the role of BDNF and its receptors in hematological malignancies are discussed. Finally, directions for future research aimed at revealing the mechanisms underlying the protective effect of BDNF in patients with these diseases are suggested.
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Affiliation(s)
- David Azoulay
- Hematology Unit and Laboratories, Galilee Medical Center, Naharia, Israel; Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
| | - Netanel A Horowitz
- Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
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16
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Wu GWY, Wolkowitz OM, Reus VI, Kang JI, Elnar M, Sarwal R, Flory JD, Abu-Amara D, Hammamieh R, Gautam A, Doyle FJ, Yehuda R, Marmar CR, Jett M, Mellon SH. Serum brain-derived neurotrophic factor remains elevated after long term follow-up of combat veterans with chronic post-traumatic stress disorder. Psychoneuroendocrinology 2021; 134:105360. [PMID: 34757255 DOI: 10.1016/j.psyneuen.2021.105360] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 07/14/2021] [Accepted: 07/15/2021] [Indexed: 10/20/2022]
Abstract
Attempts to correlate blood levels of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) have provided conflicting results. Some studies found a positive association between BDNF and PTSD diagnosis and symptom severity, while others found the association to be negative. The present study investigated whether serum levels of BDNF are different cross-sectionally between combat trauma-exposed veterans with and without PTSD, as well as whether longitudinal changes in serum BDNF differ as a function of PTSD diagnosis over time. We analyzed data of 270 combat trauma-exposed veterans (230 males, 40 females, average age: 33.29 ± 8.28 years) and found that, at the initial cross-sectional assessment (T0), which averaged 6 years after the initial exposure to combat trauma (SD=2.83 years), the PTSD positive group had significantly higher serum BDNF levels than the PTSD negative controls [31.03 vs. 26.95 ng/mL, t(268) = 3.921, p < 0.001]. This difference remained significant after excluding individuals with comorbid major depressive disorder, antidepressant users and controlling for age, gender, race, BMI, and time since trauma. Fifty-nine of the male veterans who participated at the first timepoint (T0) were re-assessed at follow-up evaluation (T1), approximately 3 years (SD=0.88 years) after T0. A one-way ANOVA comparing PTSD positive, "subthreshold PTSD" and control groups revealed that serum BDNF remained significantly higher in the PTSD positive group than the control group at T1 [30.05 vs 24.66 ng/mL, F(2, 56)= 3.420, p = 0.040]. Serum BDNF levels did not correlate with PTSD symptom severity at either time point within the PTSD group [r(128) = 0.062, p = 0.481 and r(28) = 0.157, p = 0.407]. Serum BDNF did not significantly change over time within subjects [t(56) = 1.269, p = 0.210] nor did the change of serum BDNF from T0 to T1 correlate with change in PTSD symptom severity within those who were diagnosed with PTSD at T0 [r(27) = -0.250, p = 0.192]. Our longitudinal data are the first to be reported in combat PTSD and suggest that higher serum BDNF levels may be a stable biological characteristic of chronic combat PTSD independent of symptom severity.
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Affiliation(s)
- Gwyneth W Y Wu
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
| | - Owen M Wolkowitz
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA
| | - Victor I Reus
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA
| | - Jee In Kang
- Institute of Behavioral Science in Medicine & Department of Psychiatry, Yonsei University College of Medicine, Seoul, South Korea
| | - Mathea Elnar
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA
| | - Reuben Sarwal
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA
| | - Janine D Flory
- James J Peters VA Medical Center, Bronx NY; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Duna Abu-Amara
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA
| | - Rasha Hammamieh
- Medical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD
| | - Aarti Gautam
- Medical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD
| | - Francis J Doyle
- Harvard John A. Paulson School of Engineering & Applied Sciences, Harvard University, Cambridge, MA, USA
| | - Rachel Yehuda
- James J Peters VA Medical Center, Bronx NY; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Charles R Marmar
- Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA
| | - Marti Jett
- Headquarter, Walter Reed Army Institute of Research, Silver Spring, MD
| | - Synthia H Mellon
- Department of OB-GYN and Reproductive Sciences, UCSF School of Medicine, San Francisco, CA, USA
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17
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Li X, Han T, Zou X, Zhang H, Feng W, Wang H, Shen Y, Zhang L, Fang G. Long-term high-intensity interval training increases serum neurotrophic factors in elderly overweight and obese Chinese adults. Eur J Appl Physiol 2021; 121:2773-2785. [PMID: 34148146 DOI: 10.1007/s00421-021-04746-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 06/12/2021] [Indexed: 01/14/2023]
Abstract
PURPOSE To compare the effects of 12-week high-intensity interval training (HIIT) and vigorous-intensity continuous training (VICT) on cognitive function, physical fitness, VO2max, serum neurotransmitters and neurotrophic factors in overweight and obese elderly individuals. METHODS Twenty-nine physically inactive older adults (18 males and 11 females) with a mean age of 64.8 ± 3.9 years were randomly divided into a control group (CON, n = 9), an HIIT group (4 × 3 min at 90% VO2max interspersed with 3 min at 60% VO2max, n = 10) and a VICT group (25 min at 70% VO2max, n = 10) and submitted to 12 weeks of training. Cognitive function questionnaires, physical fitness, VO2max, serum neurotransmitters and neurotrophic factors were determined at baseline and post training. RESULTS Twelve weeks of HIIT and VICT improved the VO2max (4.19 ± 2.21 and 1.84 ± 1.63 mL/kg/min, respectively, p = 0.005), sit-and-reach distance (8.7 ± 3.0 and 7.8 ± 3.8 cm, p = 0.033), choice reaction time (- 0.115 ± 0.15 and - 0.09 ± 0.15 s, p = 0.004) and one-leg stand time (4.4 ± 3.4 and 4.2 ± 4.0 s, p < 0.001) of the elderly participants. The serum concentrations of brain-derived neurotrophic factor (375.5 ± 247.9 and 227.0 ± 137.1 pg/ml, p = 0.006), nerve growth factor (33.9 ± 16.7 and 23.3 ± 14.5 pg/ml, p = 0.037), neurotrophin-3 (24.2 ± 9.33 and 16.3 ± 5.91 pg/ml, p = 0.006) and neurotrophin-4 (10.4 ± 3.8 and 7.8 ± 5.0 pg/ml, p = 0.029) increased significantly in the HIIT and VICT groups after training. In addition, compared to VICT, HIIT significantly increased VO2max and the serum neurotrophin-3 concentration. Serum concentrations of the neurotransmitters acetylcholine, dopamine and serotonin trended upward with training. No significant change was observed in the cognitive function questionnaire scores (p > 0.05). CONCLUSION HIIT is suitable for elderly adults and is more effective than VICT for improving VO2max and serum neurotrophin-3 concentrations. CHINESE CLINICAL TRIAL REGISTRY NUMBER No. ChiCTR1900022315, date of registration: 4 April 2019.
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Affiliation(s)
- Xi Li
- China Institute of Sport Science, 11 Tiyuguan Road, Dongcheng District, Beijing, 100061, China
| | - Tianyu Han
- China Institute of Sport Science, 11 Tiyuguan Road, Dongcheng District, Beijing, 100061, China
| | - Xu Zou
- Beijing Aerospace General Hospital, 7 Wanyuan North Road, Fengtai District, Beijing, 100076, China
| | - Han Zhang
- Beijing Aerospace General Hospital, 7 Wanyuan North Road, Fengtai District, Beijing, 100076, China
| | - Wenpin Feng
- China Institute of Sport Science, 11 Tiyuguan Road, Dongcheng District, Beijing, 100061, China
| | - Han Wang
- China Institute of Sport Science, 11 Tiyuguan Road, Dongcheng District, Beijing, 100061, China
| | - Yulin Shen
- China Institute of Sport Science, 11 Tiyuguan Road, Dongcheng District, Beijing, 100061, China
| | - Li Zhang
- China Institute of Sport Science, 11 Tiyuguan Road, Dongcheng District, Beijing, 100061, China.
| | - Guoliang Fang
- China Institute of Sport Science, 11 Tiyuguan Road, Dongcheng District, Beijing, 100061, China.
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18
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Perilla Seed Oil Enhances Cognitive Function and Mental Health in Healthy Elderly Japanese Individuals by Enhancing the Biological Antioxidant Potential. Foods 2021; 10:foods10051130. [PMID: 34069601 PMCID: PMC8161281 DOI: 10.3390/foods10051130] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/14/2021] [Accepted: 05/17/2021] [Indexed: 01/06/2023] Open
Abstract
Oxidative stress plays an important role in age-associated cognitive decline. We recently reported that dietary intake of perilla seed oil (PO), a rich source of α-linolenic acid (LNA, C18:3, ω-3), helps in maintaining good mental health in adults. This study aimed to investigate the impacts of dietary PO intake on cognitive functions and mental health in healthy, elderly Japanese individuals. Seventy-five healthy volunteers aged 64–84 years were randomly divided into two groups: a control group and a PO-administered group. At baseline and at 12 months of intervention, cognitive function, mental health condition, fatty acid profile of the red blood cell plasma membranes (RBC-PM), and serum biochemical parameters were evaluated. Results showed that serum biological antioxidant potential and LNA levels in the RBC-PM at 12 months after the trial were significantly higher in the PO group compared to the control group. Further, both the cognitive function measures, as evaluated by the Frontal Assessment Battery test and the apathy scores, tended to be improved after 12 months in the PO group. Our results demonstrate that dietary PO intake enhances the antioxidant potential and prevents the age-related cognitive and mental decline in healthy elderly individuals by enhancing the blood LNA levels.
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19
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Galle S, Licher S, Milders M, Deijen JB, Scherder E, Drent M, Ikram A, van Duijn CM. Plasma Brain-Derived Neurotropic Factor Levels Are Associated with Aging and Smoking But Not with Future Dementia in the Rotterdam Study. J Alzheimers Dis 2021; 80:1139-1149. [PMID: 33646145 PMCID: PMC8150496 DOI: 10.3233/jad-200371] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Brain-derived neurotropic factor (BDNF) plays a vital role in neuronal survival and plasticity and facilitates long-term potentiation, essential for memory. Alterations in BDNF signaling have been associated with cognitive impairment, dementia, and Alzheimer's disease. Although peripheral BDNF levels are reduced in dementia patients, it is unclear whether changes in BDNF levels precede or follow dementia onset. OBJECTIVE In the present study, we examined the association between BDNF plasma levels and dementia risk over a follow-up period of up to 16 years. METHODS Plasma BDNF levels were assessed in 758 participants of the Rotterdam Study. Dementia was assessed from baseline (1997-1999) to follow-up until January 2016. Associations of plasma BDNF and incident dementia were assessed with Cox proportional hazards models, adjusted for age and sex. Associations between plasma BDNF and lifestyle and metabolic factors are investigated using linear regression. RESULTS During a follow up of 3,286 person-years, 131 participants developed dementia, of whom 104 had Alzheimer's disease. We did not find an association between plasma BDNF and risk of dementia (adjusted hazard ratio 0.99; 95%CI 0.84-1.16). BDNF levels were positively associated with age (B = 0.003, SD = 0.001, p = 0.002), smoking (B = 0.08, SE = 0.01, p = < 0.001), and female sex (B = 0.03, SE = 0.01, p = 0.03), but not with physical activity level (B = -0.01, SE = 0.01, p = 0.06). CONCLUSION The findings suggest that peripheral BDNF levels are not associated with an increased risk of dementia.
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Affiliation(s)
- Sara Galle
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Silvan Licher
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Maarten Milders
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Jan Berend Deijen
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Hersencentrum Mental Health Institute, Amsterdam, The Netherlands
| | - Erik Scherder
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Madeleine Drent
- Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Department of Internal Medicine, Endocrinology Section, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Arfan Ikram
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Cornelia M. van Duijn
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
- Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, United Kingdom
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20
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Neuroprotective Biomarkers and Cognitive Function in a Long-Term Prospective Population-based Study of Aging US Adults. Alzheimer Dis Assoc Disord 2020; 34:31-39. [PMID: 31385821 DOI: 10.1097/wad.0000000000000341] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Relationships between brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), aldosterone, and cognition in aging were evaluated in the population-based Epidemiology of Hearing Loss Study (1993 to present). METHODS Beginning in 1998 to 2000, cognitive impairment was assessed by report of physician diagnoses and the Mini-Mental State Examination. In 2009 to 2010 and 2013 to 2016, information was collected on diagnosis of mild cognitive impairment/dementia. Decline in cognitive function was assessed by principal component analysis from additional tests administered during 2009 to 2010 and 2013 to 2016. BDNF, IGF-1, and aldosterone were measured in serum collected in 1998 to 2000. RESULTS There were 1970 participants (mean age=66.9 y; 59.1% female) without cognitive impairment at baseline. Among women, low BDNF was associated with 16-year incident cognitive impairment [hazard ratio=1.76; 95% confidence interval (CI)=1.04, 2.98]. Among men, increasing IGF-1 was associated with decreased risk [per SD: relative risk (RR)=0.57; 95% CI=0.35, 0.92], whereas increasing aldosterone levels were associated with increased risk (per SD: RR=1.28; 95% CI=1.01, 1.62) for 5-year incident mild cognitive impairment/dementia. Overall, low BDNF was associated with increased risk (RR=1.52; 95% CI=1.02, 2.26) for 5-year cognitive decline. CONCLUSION Low levels of serum BDNF and IGF-1 were associated with poorer cognition during aging. There may be differential biomarker effects by sex.
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21
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McPhee GM, Downey LA, Stough C. Neurotrophins as a reliable biomarker for brain function, structure and cognition: A systematic review and meta-analysis. Neurobiol Learn Mem 2020; 175:107298. [PMID: 32822863 DOI: 10.1016/j.nlm.2020.107298] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 08/02/2020] [Accepted: 08/14/2020] [Indexed: 01/04/2023]
Abstract
Neurotrophins are signalling molecules involved in the formation and maintenance of synapses in the brain. They can cross the blood-brain barrier and be detected in peripheral blood, suggesting they may be a potential biomarker for brain health and function. In this review, the available literature was systematically searched for studies comparing peripheral neurotrophins levels with MRI and cognitive measures in healthy adults. Twenty-four studies were identified, six of which included a neuroimaging outcome. Fifteen studies measuring cognition were eligible for meta-analysis. The majority of studies measured levels of brain-derived neurotrophic factor (BDNF), with few assessing other neurotrophins. Results revealed BDNF is related to some neuroimaging outcomes, with some studies suggesting older age may be an important factor. A higher proportion of studies who had older samples observed significant effects between cognition and neurotrophin levels. When cognitive studies were pooled together in a meta-analysis, there was a weak non-significant effect between BDNF and cognitive outcomes. There was also a high level of heterogeneity between cognitive studies. Results indicated that gender was a notable source of the heterogeneity, but additional studies employing relevant covariates are necessary to better characterise the inter-relationship between circulating neurotrophins and cognition.
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Affiliation(s)
- Grace M McPhee
- Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia
| | - Luke A Downey
- Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia; Institute for Breathing and Sleep, Austin Health, Melbourne, Australia
| | - Con Stough
- Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia
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22
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Ismail NA, Leong Abdullah MFI, Hami R, Ahmad Yusof H. A narrative review of brain-derived neurotrophic factor (BDNF) on cognitive performance in Alzheimer's disease. Growth Factors 2020; 38:210-225. [PMID: 33427532 DOI: 10.1080/08977194.2020.1864347] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is highly expressed in the brain. It influences neuronal survival, growth and acts as a control centre for neurotransmitters. It also plays a crucial role in learning and memory. Current evidence indicates that BDNF may be a possible neurotrophic factor that controls cognitive functions under normal and neuropathological conditions. Recent findings indicate a reduction in cognitive performance in individuals with Alzheimer's disease (AD). This relationship between cognitive performance and AD is important for investigating both the time they overlap and the pathophysiological mechanism in each case. Therefore, this study reviewed the existing knowledge about BDNF and cognitive performance in the AD population. The findings support the idea that this tropic factor may be a potential biomarker for evaluating the changes in cognitive performance in AD.
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Affiliation(s)
- Noor Azila Ismail
- Institut Perubatan dan Pengigian Termaju, Lifestyle Science Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia
| | - Mohammad Farris Iman Leong Abdullah
- Institut Perubatan dan Pengigian Termaju, Lifestyle Science Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia
| | - Rohayu Hami
- Institut Perubatan dan Pengigian Termaju, Lifestyle Science Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia
| | - Hazwani Ahmad Yusof
- Institut Perubatan dan Pengigian Termaju, Lifestyle Science Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia
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Bharani KL, Ledreux A, Gilmore A, Carroll SL, Granholm AC. Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer's disease. Neurobiol Aging 2020; 87:49-59. [PMID: 31882186 DOI: 10.1016/j.neurobiolaging.2019.11.010] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 11/02/2019] [Accepted: 11/15/2019] [Indexed: 12/15/2022]
Abstract
Disruption of brain-derived neurotrophic factor (BDNF) biosynthesis and/or signaling has been implicated in the pathogenesis of Alzheimer's disease (AD). We used postmortem brain and fluid samples from 20 patients with variable severity of AD and 11 controls to investigate whether BDNF levels in serum and brain tissue correlated with hippocampal pathology. Total BDNF, precursor BDNF (pro-BDNF), and mature BDNF were measured in cerebrospinal fluid, serum, and 3 postmortem brain regions. Histological markers for AD pathology, the BDNF cognate receptor (TrkB), and glia were measured in the hippocampus (HIP). Lower pro-BDNF levels were observed in the entorhinal and frontal cortices in AD cases compared with controls. AD cases also exhibited significantly lower staining densities of the cognate BDNF receptor TrkB in the HIP compared with controls, and TrkB staining was inversely correlated with both Amylo-Glo and pTau staining in the same region, suggesting a relationship between the density of the cognate BDNF receptor and accumulation of AD pathology. In addition, higher serum pro-BDNF levels correlated with lower HIP pro-BDNF levels and higher pTau staining in the HIP. Total BDNF levels in cortical regions were also negatively correlated with Amylo-Glo staining in the HIP suggesting that reduced BDNF cortical levels might influence hippocampal amyloid accumulation. These results strongly suggest that altered BDNF and TrkB receptors are involved in AD pathology and therefore warrant investigations into therapies involving the BDNF pathway.
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Affiliation(s)
- Krishna L Bharani
- Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
| | - Aurélie Ledreux
- Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA
| | - Anah Gilmore
- Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA
| | - Steven L Carroll
- Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Ann-Charlotte Granholm
- Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA; Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA.
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Modification of Serum Brain-Derived Neurotrophic Factor Levels Following Anti-HCV Therapy with Direct Antiviral Agents: A New Marker of Neurocognitive Disorders. HEPATITIS MONTHLY 2020. [DOI: 10.5812/hepatmon.95101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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25
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Brain-derived neurotrophic factor in heart failure. Anatol J Cardiol 2019; 22:317-318. [PMID: 31789615 PMCID: PMC6955040 DOI: 10.14744/anatoljcardiol.2019.49393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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26
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Mravunac M, Szymlek-Gay EA, Daly RM, Roberts BR, Formica M, Gianoudis J, O'Connell SL, Nowson CA, Cardoso BR. Greater Circulating Copper Concentrations and Copper/Zinc Ratios are Associated with Lower Psychological Distress, But Not Cognitive Performance, in a Sample of Australian Older Adults. Nutrients 2019; 11:nu11102503. [PMID: 31627408 PMCID: PMC6836146 DOI: 10.3390/nu11102503] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 10/10/2019] [Accepted: 10/10/2019] [Indexed: 02/06/2023] Open
Abstract
Dyshomeostasis of copper and zinc is linked to neurodegeneration. This study investigated the relationship between circulating copper and zinc and copper/zinc ratios and cognitive function, symptoms of depression and anxiety, and neurotrophic factors in older Australian adults. In this cross-sectional study (n = 139), plasma copper, serum zinc, and neurotrophic factors (brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and insulin-like growth factor-1) were assessed. Cognition was assessed using the Cogstate battery and the Behavior Rating Inventory (BRI) of Executive Function (Adult version). Symptoms of anxiety and depression were assessed with the Hospital Anxiety and Depression Scale. Copper (β = −0.024; 95% CI = −0.044, −0.004; p = 0.019) and copper/zinc ratio (β = −1.99; 95% CI = −3.41, −0.57; p = 0.006) were associated with lower depressive symptoms, but not cognition. Plasma copper had a modest positive association with BDNF (β = −0.004; 95% CI = 0.000, 0.007; p = 0.021). Zinc was not associated with any of the outcomes. In conclusion, greater circulating copper concentrations and higher copper/zinc ratios were associated with lower depressive symptoms (but not cognition), with copper also positively associated with BDNF concentration, in a sample of community-dwelling older adults.
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Affiliation(s)
- Michelle Mravunac
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
| | - Ewa A Szymlek-Gay
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
- Nutrition Society of Australia, PO Box 576, Crows Nest, NSW 1585, Australia.
| | - Robin M Daly
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
| | - Blaine R Roberts
- Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia.
| | - Melissa Formica
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
| | - Jenny Gianoudis
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
| | - Stella L O'Connell
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
| | - Caryl A Nowson
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
- Nutrition Society of Australia, PO Box 576, Crows Nest, NSW 1585, Australia.
| | - Barbara R Cardoso
- Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC 3220, Australia.
- Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia.
- Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, VIC 3128, Australia.
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Hassan TM, Yarube IU. Peripheral brain-derived neurotrophic factor is reduced in stroke survivors with cognitive impairment. PATHOPHYSIOLOGY 2018; 25:405-410. [DOI: 10.1016/j.pathophys.2018.08.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 07/09/2018] [Accepted: 08/10/2018] [Indexed: 11/25/2022] Open
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Barha CK, Liu-Ambrose T, Best JR, Yaffe K, Rosano C. Sex-dependent effect of the BDNF Val66Met polymorphism on executive functioning and processing speed in older adults: evidence from the health ABC study. Neurobiol Aging 2018; 74:161-170. [PMID: 30448615 DOI: 10.1016/j.neurobiolaging.2018.10.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 10/14/2018] [Accepted: 10/16/2018] [Indexed: 02/07/2023]
Abstract
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may be an important source of heterogeneity seen in cognitive aging, although the specific relationship between this polymorphism and cognition remains controversial and may depend on the sex of participants. We assessed 2668 older black and white adults and fit linear mixed models to digit symbol substitution test (DSST) performance assessed in years 0 (baseline), 4, 7, and 9 to examine the interaction between sex and BDNF genotype on the intercept (i.e., estimated baseline DSST) and change in DSST over 9 years, adjusted for covariates. Sex interacted with BDNF genotype to predict DSST intercept (F[1,1599] = 7.4, p < 0.01) and 9-year change (F[1,1183] = 4.1, p = 0.04) in white participants only. Initially, white male Val/Val carriers had lower DSST scores (37.6, SE = 0.8) in comparison with male Met carriers (difference, -1.7; 95% CI, -3.2 to -0.3) and female Val/Val carriers (difference, -5.6; 95% CI, -6.8 to -4.3). White female Met carriers showed a slower rate of change (annual rate of change = -0.6, SE = 0.1) in comparison with female Val/Val carriers (difference, -0.2; 95% CI, -0.4 to -0.02) and male Met carriers (difference, -0.3; 95% CI, -0.5 to -0.02). Our findings suggest that BDNF Val66Met and sex should be considered in future endeavors aimed at treating or preventing neurodegenerative disorders.
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Affiliation(s)
- Cindy K Barha
- Djavad Mowafaghian Centre for Brain Health, Vancouver Coastal Health Research Institute, Vancouver, Canada; Department of Physical Therapy, University of British Columbia, Vancouver, Canada.
| | - Teresa Liu-Ambrose
- Djavad Mowafaghian Centre for Brain Health, Vancouver Coastal Health Research Institute, Vancouver, Canada; Department of Physical Therapy, University of British Columbia, Vancouver, Canada; Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, Canada
| | - John R Best
- Djavad Mowafaghian Centre for Brain Health, Vancouver Coastal Health Research Institute, Vancouver, Canada; Department of Physical Therapy, University of British Columbia, Vancouver, Canada
| | - Kristine Yaffe
- Department of Epidemiology and Biostatistics, University of California, San Francisco, USA; Departments of Psychiatry and Neurology, University of California, San Francisco, USA
| | - Caterina Rosano
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, USA
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Fernandes RM, Correa MG, Dos Santos MAR, Almeida APCPSC, Fagundes NCF, Maia LC, Lima RR. The Effects of Moderate Physical Exercise on Adult Cognition: A Systematic Review. Front Physiol 2018; 9:667. [PMID: 29937732 PMCID: PMC6002532 DOI: 10.3389/fphys.2018.00667] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 05/14/2018] [Indexed: 12/22/2022] Open
Abstract
Background: Physical exercise is a systematic sequence of movements executed with a predefined purpose. This muscular activity impacts not only on circulatory adaptations, but also neuronal integration with the potential to influence cognition. The aim of this review was to determine whether the literature supports the idea that physical exercise promotes cognitive benefits in healthy adults. Methods: A systematic search for relevant articles was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria using available databases (PubMed, LILACS, Scopus, Web of Science, The Cochrane Library, OpenGrey, Google Scholar and CENTRAL). The search terms included “humans” or “adults” or “cognition” or “awareness” or “cognitive dissonance” or “cognitive reserve” or “comprehension” or “consciousness” and “motor activity” or “exercise” or “physical fitness,” and not “aged” or “nervous system diseases,” with the purpose of finding associations between moderate physical exercise and cognition. A methodological quality and risk of bias unit assessed the eligibility of articles. Results: A total of 7179 articles were identified. Following review and quality assessment, three articles were identified to fulfill the inclusion criteria. An association between moderate physical exercise and cognition was observed. Improvements in cognitive parameters such as reduced simple reaction time, improved response precision and working memory were identified among the included articles. Conclusion: This systematic review found that moderate physical exercise improves cognition.
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Affiliation(s)
- Rafael M Fernandes
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Marcio G Correa
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Marcio A R Dos Santos
- Nucleus of Transdisciplinary Studies in Basic Education, Federal University of Pará, Belém, Brazil
| | - Anna P C P S C Almeida
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Nathália C F Fagundes
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
| | - Lucianne C Maia
- Pediatric Dentistry and Orthodontics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Rafael R Lima
- Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil
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30
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Weinstein G, Preis SR, Beiser AS, Kaess B, Chen TC, Satizabal C, Rahman F, Benjamin EJ, Vasan RS, Seshadri S. Clinical and Environmental Correlates of Serum BDNF: A Descriptive Study with Plausible Implications for AD Research. Curr Alzheimer Res 2018; 14:722-730. [PMID: 28164772 DOI: 10.2174/1567205014666170203094520] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 12/13/2016] [Accepted: 01/27/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Brain derived neurotrophic factor (BDNF) may play a central role in the pathogenesis of Alzheimer's disease (AD) through neurotrophic effects on basal cholinergic neurons. Reduced serum levels of BDND are observed among AD patients and may predict AD risk. Nevertheless, knowledge about factors associated with its levels in blood is lacking. OBJECTIVE To identify clinical and demographic correlates of serum BDNF levels. METHODS BDNF was measured from serum collected between 1992-1996 and 1998-2001 in participants from the Original and Offspring cohorts of the Framingham Study, respectively. A cross-sectional analysis was done to evaluate the relationship between clinical measures and BDNF levels using standard linear regression and stepwise models. Analyses were conducted in the total sample and separately in each cohort, and were adjusted for age and sex. RESULTS BDNF was measured in 3,689 participants (mean age 65 years, 56% women; 82% Offspring). Cigarette smoking and high total cholesterol were associated with elevated BDNF levels, and history of atrial fibrillation was associated with decreased levels. Elevated BDNF levels were related to greater physical activity and lower Tumor Necrosis Factor-α levels in Offspring. Stepwise models also revealed associations with statin use, alcohol consumption and Apolipoprotein Eε4 genotype. CONCLUSION Serum BDNF correlates with various metabolic, inflammatory and life-style measures which in turn have been linked with risk of AD. Future studies of serum BDNF should adjust for these correlates and are needed to further explore the underlying interplay between BDNF and other factors in the pathophysiology of cognitive impairment and AD.
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Affiliation(s)
- Galit Weinstein
- School of Public Health, University of Haifa, 199 Aba Khoushy Ave., Mount Carmel, Haifa. Israel
| | | | - Alexa S Beiser
- The Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
| | | | - Tai C Chen
- The Department of Neurology, Boston University School of Medicine, Boston, MA, United States
| | - Claudia Satizabal
- The Department of Neurology, Boston University School of Medicine, Boston, MA, United States
| | - Faisal Rahman
- The Department of Medicine, Boston University School of Medicine, Boston, MA, United States
| | - Emelia J Benjamin
- The Department of Epidemiology, Boston University School of Public Health, Boston, MA, Boston, United States
| | - Ramachandran S Vasan
- The Department of Epidemiology, Boston University School of Public Health, Boston, MA, Boston, United States
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31
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Ng T, Lee YY, Chae JW, Yeo AHL, Shwe M, Gan YX, Ng RCH, Chu PPY, Khor CC, Ho HK, Chan A. Evaluation of plasma brain-derived neurotrophic factor levels and self-perceived cognitive impairment post-chemotherapy: a longitudinal study. BMC Cancer 2017; 17:867. [PMID: 29258453 PMCID: PMC5735945 DOI: 10.1186/s12885-017-3861-9] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 11/29/2017] [Indexed: 12/18/2022] Open
Abstract
Background Preliminary evidence suggests that changes in plasma brain-derived neurotrophic factor (BDNF) levels may contribute to the occurrence of chemotherapy-associated cognitive impairment (CACI), and a previous study suggested that carriers of the BDNF Met homozygous genotype are protected from CACI. Methods This multicenter, prospective cohort study involved chemotherapy-receiving early-stage breast cancer (ESBC) patients. Self-perceived cognitive function was longitudinally assessed using the validated FACT-Cog (ver. 3) across three time points: Prior to chemotherapy (T1), during chemotherapy (T2), and at the end of chemotherapy (T3). Plasma BDNF levels were quantified using enzyme-linked immunosorbent assay. Genotyping was performed using Sanger Sequencing. Results A total of 51 chemotherapy-receiving ESBC patients (mean age: 52.6 ± 9.5 years) were recruited, and 11 patients (21.6%) reported subjective cognitive impairment post-chemotherapy. Overall, there was a reduction in median plasma BDNF levels over time (T1: 5423.0 pg/ml; T2: 5313.6 pg/ml; T3: 4050.3 pg/ml; p < 0.01). After adjusting for confounding factors, longitudinal analysis revealed that BDNF levels were associated with self-reported concentration deficit (p = 0.032). Carriers of Val/Val (p = 0.011) and Val/Met (p = 0.003) BDNF genotypes demonstrated a significant reduction in plasma BDNF levels over time; however, plasma BDNF levels were similar across all time points among Met homozygous carriers (p = 0.107). Conclusion There was a statistically significant change in BDNF levels post-chemotherapy in ESBC patients, and plasma BDNF levels were associated with self-perceived concentration deficit in patients receiving chemotherapy.
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Affiliation(s)
- Terence Ng
- Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore.,Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore
| | - Ying Yun Lee
- Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore
| | - Jung-Woo Chae
- Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore.,Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore
| | - Angie Hui Ling Yeo
- Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore
| | - Maung Shwe
- Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore
| | - Yan Xiang Gan
- Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore
| | - Raymond C H Ng
- Duke-NUS Medical School Singapore, Singapore, Singapore.,Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Pat Pak Yan Chu
- Singapore Cord Blood Bank, K.K. Women's and Children's Hospital, Singapore, Singapore
| | | | - Han Kiat Ho
- Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore
| | - Alexandre Chan
- Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore. .,Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore. .,Duke-NUS Medical School Singapore, Singapore, Singapore.
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Binford SS, Hubbard EM, Flowers E, Miller BL, Leutwyler H. Serum BDNF Is Positively Associated With Negative Symptoms in Older Adults With Schizophrenia. Biol Res Nurs 2017; 20:63-69. [PMID: 29050493 DOI: 10.1177/1099800417735634] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Older adults with chronic schizophrenia are at greater risk for functional disability and poorer health outcomes than those without serious mental illness. These individuals comprise 1-2% of the elderly population in the United States and are projected to number approximately 15 million by 2030. The symptoms of schizophrenia can be disabling for individuals, significantly reducing quality of life. Often, the negative symptoms (NS) are the most resistant to treatment and are considered a marker of illness severity, though they are challenging to measure objectively. Biomarkers can serve as objective indicators of health status. Brain-derived neurotrophic factor (BDNF) is a potential biomarker for schizophrenia and may serve as an important indicator of illness severity. METHODS A cross-sectional study with 30 older adults with chronic schizophrenia. Participants were assessed on serum levels of BDNF and psychiatric symptoms (Positive and Negative Syndrome Scale). Pearson's bivariate correlations (two-tailed) and linear regression models were used. RESULTS A significant positive association ( p < .05) was found between higher serum levels of BDNF and greater severity for the NS items of passive, apathetic, social withdrawal, and emotional withdrawal. In multivariate analyses, the association remained significant. CONCLUSIONS Although the association between BDNF and NS was not in the expected direction, the data corroborate findings from previous work in patients with schizophrenia. It is possible that higher serum levels of BDNF reflect compensatory neuronal mechanisms resulting from neurodevelopmental dysfunction.
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Affiliation(s)
- Sasha S Binford
- 1 Memory and Aging Center, University of California, San Francisco, CA, USA.,2 Department of Physiological Nursing, University of California, San Francisco, CA, USA
| | - Erin M Hubbard
- 2 Department of Physiological Nursing, University of California, San Francisco, CA, USA
| | - Elena Flowers
- 3 Department of Physiological Nursing, Institute for Human Genetics, University of California, San Francisco, CA, USA
| | - Bruce L Miller
- 1 Memory and Aging Center, University of California, San Francisco, CA, USA
| | - Heather Leutwyler
- 2 Department of Physiological Nursing, University of California, San Francisco, CA, USA
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Walsh JJ, Bentley RF, Gurd BJ, Tschakovsky ME. Short-Duration Maximal and Long-Duration Submaximal Effort Forearm Exercise Achieve Elevations in Serum Brain-Derived Neurotrophic Factor. Front Physiol 2017; 8:746. [PMID: 29056915 PMCID: PMC5635651 DOI: 10.3389/fphys.2017.00746] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 09/12/2017] [Indexed: 01/08/2023] Open
Abstract
Brain-derived neurotrophic factor (BDNF) is a major orchestrator of exercise-induced brain plasticity and circulating (peripheral) BDNF may have central effects. Approximately 99% of circulating BDNF is platelet-bound, and at rest ~30% of circulating platelets are stored in the spleen. Interestingly, forearm handgrip exercise significantly elevates sympathetic outflow and has been shown to induce splenic constriction, suggesting that small muscle mass exercise could stand as a viable strategy for increasing circulating BDNF; however, the BDNF response to handgrip exercise is currently unknown. Purpose: This study examined BDNF and platelet responses to short-duration maximal (ME) and prolonged submaximal (SE) effort handgrip exercise. Methods: Healthy males (n = 18; 21.4 ± 2.1 years, BMI 25.0 ± 1.0 kg/m2) performed 10 min of ME and 30 min of SE. Blood was sampled for the determination of serum BDNF and platelet count at rest and during the last minute of exercise. Results: Compared to rest, serum BDNF significantly increased during ME (21.2%) and SE (11.2%), which displayed a non-significant trend toward an intensity-dependent response. Platelets increased in an intensity-dependent fashion compared to rest with an 8.0% increase during ME and 3.1% during SE, and these responses were significantly correlated with diastolic blood pressure responses to handgrip exercise. Further, the amount of BDNF per platelet significantly increased compared to rest during ME (13.4%) and SE (8.7%). Conclusions: Handgrip exercise evokes significant increases in serum BDNF and platelets, implicating splenic constriction as a key mechanism and confirming efficacy of this exercise model for elevating circulating BDNF.
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Affiliation(s)
- Jeremy J Walsh
- Human Vascular Control Lab, School of Kinesiology and Health Studies, Queen's University, Kingston, ON, Canada
| | - Robert F Bentley
- Human Vascular Control Lab, School of Kinesiology and Health Studies, Queen's University, Kingston, ON, Canada
| | - Brendon J Gurd
- Queen's Muscle Physiology Lab, School of Kinesiology and Health Studies, Queen's University, Kingston, ON, Canada
| | - Michael E Tschakovsky
- Human Vascular Control Lab, School of Kinesiology and Health Studies, Queen's University, Kingston, ON, Canada
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34
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Hvid LG, Nielsen MKF, Simonsen C, Andersen M, Caserotti P. Brain-derived neurotrophic factor (BDNF) serum basal levels is not affected by power training in mobility-limited older adults - A randomized controlled trial. Exp Gerontol 2017; 93:29-35. [PMID: 28392271 DOI: 10.1016/j.exger.2017.03.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 01/28/2017] [Accepted: 03/13/2017] [Indexed: 12/21/2022]
Abstract
Brain-derived neurotrophic factor (BDNF) is a potential important factor involved in neuroplasticity, and may be a mediator for eliciting adaptations in neuromuscular function and physical function in older individuals following physical training. As power training taxes the neural system to a very high extent, it may be particularly effective in terms of eliciting increases in systemic BDNF levels. We examined the effects of 12weeks of power training on mature BDNF (mBDNF) and total BDNF (tBDNF) in mobility-limited older adults from the Healthy Ageing Network of Competence (HANC) study. We included 47 older men and women: n=22 in the training group (TG: progressive high intensity power training, 2 sessions per week; age 82.7±5.4years, 55% women) and n=25 in the control group (CG: no interventions; age 82.2±4.5years, 76% women). Following overnight fasting, basal serum levels of mBDNF and tBDNF were assessed (human ELISA kits) at baseline and post-intervention. At baseline, mBDNF and tBDNF levels were comparable in the two groups, TG and CG. Post-intervention, no significant within-group or between-group changes were observed in mBDNF or tBDNF. Moreover, when divided into responder tertiles based upon changes in mBDNF and tBDNF (i.e. decliners, maintainers, improvers), respectively, comparable findings were observed for TG and CG. Altogether, basal systemic levels of serum mBDNF and tBDNF are not affected in mobility-limited older adults following 12-weeks of power training, and do not appear to be a major mechanistic factor mediating neuroplasticity in mobility-limited older adults.
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Affiliation(s)
- L G Hvid
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark (SDU), Odense, Denmark.
| | - M K F Nielsen
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark (SDU), Odense, Denmark
| | - C Simonsen
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark (SDU), Odense, Denmark
| | - M Andersen
- Department of Endocrinology, Odense University Hospital, Odense, Denmark
| | - P Caserotti
- Department of Sports Science and Clinical Biomechanics, University of Southern Denmark (SDU), Odense, Denmark; National Institutes of Health, National Institute on Aging, Laboratory of Epidemiology and Population Sciences (LPES), Bethesda, MD, United States
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Diz JBM, de Souza Moreira B, Felício DC, Teixeira LF, de Jesus-Moraleida FR, de Queiroz BZ, Pereira DS, Pereira LSM. Brain-derived neurotrophic factor plasma levels are increased in older women after an acute episode of low back pain. Arch Gerontol Geriatr 2017; 71:75-82. [PMID: 28376368 DOI: 10.1016/j.archger.2017.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 03/08/2017] [Accepted: 03/17/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND Low back pain (LBP) is a growing public health problem in old age, and it is associated with disabling pain and depressive disorders. We compared brain-derived neurotrophic factor (BDNF) plasma levels, a key neurotrophin in pain modulation, between older women after an acute episode of LBP and age-matched pain-free controls, and investigated potential differences in BDNF levels between controls and LBP subgroups based on pain severity, presence of depressive symptoms and use of analgesic and antidepressant drugs. METHODS A total of 221 participants (154 with LBP and 67 pain-free) were studied. A comprehensive assessment of sociodemographic and clinical variables was conducted including pain severity (11-point NRS), depressive symptoms (GDS-15), age, body mass index, physical activity and total number of comorbidities and medications in use. RESULTS BDNF levels in LBP group were significantly higher than controls (7515.9±3021.2; Md=7116.0 vs 6331.8±3364.0; Md=5897.5pg/mL, P=0.005). LBP subgroups exhibited higher BDNF levels than controls, regardless of pain severity, presence of depressive symptoms and use of analgesic drugs. BDNF levels were significantly higher in LBP subgroup without use of antidepressant drugs compared to both controls and LBP subgroup with use of antidepressant drugs. DISCUSSION This study provides evidence that older women with acute low back pain exhibit higher BDNF plasma levels compared to pain-free controls. Subgroup comparisons suggest that use of pain-relief drugs may influence BDNF levels. The study results offer a novel target for research on mechanisms of back pain in older adults.
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Affiliation(s)
- Juliano Bergamaschine Mata Diz
- Department of Physical Therapy, Postgraduate Program in Rehabilitation Sciences, Universidade Federal de Minas Gerais, 6627 Antônio Carlos Avenue, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
| | - Bruno de Souza Moreira
- Department of Physical Therapy, Postgraduate Program in Rehabilitation Sciences, Universidade Federal de Minas Gerais, 6627 Antônio Carlos Avenue, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
| | - Diogo Carvalho Felício
- Department of Physical Therapy, Universidade Federal de Juiz de Fora, s/n Eugênio do Nascimento Avenue, 36038-330, Juiz de Fora, Minas Gerais, Brazil.
| | - Luiza Faria Teixeira
- Department of Physical Therapy, Universidade do Vale do Sapucaí, 320 Coronel Alfredo Custódio de Paula Avenue, 37550-000, Pouso Alegre, Minas Gerais, Brazil.
| | - Fabianna Resende de Jesus-Moraleida
- Department of Physical Therapy, Faculty of Medicine, Universidade Federal do Ceará, 949 Alexandre Barúna Street, 60430-160, Fortaleza, Ceará, Brazil.
| | - Bárbara Zille de Queiroz
- Department of Physical Therapy, Postgraduate Program in Rehabilitation Sciences, Universidade Federal de Minas Gerais, 6627 Antônio Carlos Avenue, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
| | - Daniele Sirineu Pereira
- Department of Physical Therapy, Universidade Federal de Alfenas, 2600 Jovino Fernandes Sales Avenue, 31270-901, Alfenas, Minas Gerais, Brazil.
| | - Leani Souza Máximo Pereira
- Department of Physical Therapy, Postgraduate Program in Rehabilitation Sciences, Universidade Federal de Minas Gerais, 6627 Antônio Carlos Avenue, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
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Munoz MJ, Kumar RG, Oh BM, Conley YP, Wang Z, Failla MD, Wagner AK. Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study. Front Mol Neurosci 2017; 10:44. [PMID: 28337122 PMCID: PMC5343043 DOI: 10.3389/fnmol.2017.00044] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2016] [Accepted: 02/09/2017] [Indexed: 01/04/2023] Open
Abstract
Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0–6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in “younger patients” (<48 years) and hypothesized BDNF production/secretion capacity with these variants. Group based trajectory analysis (TRAJ) was used to create two cortisol groups (high and low trajectories). A Bayesian estimation approach informed the mediation models. Results show CSF BDNF predicted patient cortisol TRAJ group (P = 0.001). Also, GRS moderated BDNF associations with cortisol TRAJ group. Additionally, cortisol TRAJ predicted 6-month mortality (P = 0.001). In a mediation analysis, BDNF predicted mortality, with cortisol acting as the mediator (P = 0.011), yielding a mediation percentage of 29.92%. Mediation effects increased to 45.45% among younger patients. A BDNF*GRS interaction predicted mortality in younger patients (P = 0.004). Thus, we conclude 6-month mortality after severe TBI can be predicted through a mediation model with CSF cortisol and BDNF, suggesting a regulatory role for cortisol with BDNF's contribution to TBI pathophysiology and mortality, particularly among younger individuals with severe TBI. Based on the literature, cortisol modulated BDNF effects on mortality after TBI may be related to known hormone and neurotrophin relationships to neurological injury severity and autonomic nervous system imbalance.
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Affiliation(s)
- Miranda J Munoz
- Department of Physical Medicine and Rehabilitation, University of PittsburghPittsburgh, PA, USA; Department of Biological Sciences, Carnegie Mellon UniversityPittsburgh, PA, USA
| | - Raj G Kumar
- Department of Physical Medicine and Rehabilitation, University of PittsburghPittsburgh, PA, USA; Department of Epidemiology, University of PittsburghPittsburgh, PA, USA
| | - Byung-Mo Oh
- Department of Physical Medicine and Rehabilitation, University of PittsburghPittsburgh, PA, USA; Department of Rehabilitation Medicine, Seoul National University HospitalSeoul, South Korea
| | - Yvette P Conley
- Department of Physical Medicine and Rehabilitation, University of PittsburghPittsburgh, PA, USA; Department of Epidemiology, University of PittsburghPittsburgh, PA, USA
| | - Zhensheng Wang
- Department of Nursing, University of PittsburghPittsburgh, PA, USA; Safar Center for Resuscitation Research, University of PittsburghPittsburgh, PA, USA
| | - Michelle D Failla
- Department of Psychiatry, Vanderbilt University Medical Center Nashville, TN, USA
| | - Amy K Wagner
- Department of Physical Medicine and Rehabilitation, University of PittsburghPittsburgh, PA, USA; Safar Center for Resuscitation Research, University of PittsburghPittsburgh, PA, USA; Department of Neuroscience, University of PittsburghPittsburgh, PA, USA; Center for Neuroscience, University of PittsburghPittsburgh, PA, USA
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Qin XY, Cao C, Cawley NX, Liu TT, Yuan J, Loh YP, Cheng Y. Decreased peripheral brain-derived neurotrophic factor levels in Alzheimer's disease: a meta-analysis study (N=7277). Mol Psychiatry 2017; 22:312-320. [PMID: 27113997 DOI: 10.1038/mp.2016.62] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 02/10/2016] [Accepted: 03/07/2016] [Indexed: 12/30/2022]
Abstract
Studies suggest that dysfunction of brain-derived neurotrophic factor (BDNF) is a possible contributor to the pathology and symptoms of Alzheimer's disease (AD). Several studies report reduced peripheral blood levels of BDNF in AD, but findings are inconsistent. This study sought to quantitatively summarize the clinical BDNF data in patients with AD and mild cognitive impairment (MCI, a prodromal stage of AD) with a meta-analytical technique. A systematic search of Pubmed, PsycINFO and the Cochrane Library identified 29 articles for inclusion in the meta-analysis. Random-effects meta-analysis showed that patients with AD had significantly decreased baseline peripheral blood levels of BDNF compared with healthy control (HC) subjects (24 studies, Hedges' g=-0.339, 95% confidence interval (CI)=-0.572 to -0.106, P=0.004). MCI subjects showed a trend for decreased BDNF levels compared with HC subjects (14 studies, Hedges' g=-0.201, 95% CI=-0.413 to 0.010, P=0.062). No differences were found between AD and MCI subjects in BDNF levels (11 studies, Hedges' g=0.058, 95% CI=-0.120 to 0.236, P=0.522). Interestingly, the effective sizes and statistical significance improved after excluding studies with reported medication in patients (between AD and HC: 18 studies, Hedges' g=-0.492, P<0.001; between MCI and HC: 11 studies, Hedges' g=-0.339, P=0.003). These results strengthen the clinical evidence that AD or MCI is accompanied by reduced peripheral blood BDNF levels, supporting an association between the decreasing levels of BDNF and the progression of AD.
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Affiliation(s)
- X-Y Qin
- Section on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - C Cao
- Section on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - N X Cawley
- Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - T-T Liu
- Section on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - J Yuan
- Section on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - Y P Loh
- Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Y Cheng
- Section on Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
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Håkansson K, Ledreux A, Daffner K, Terjestam Y, Bergman P, Carlsson R, Kivipelto M, Winblad B, Granholm AC, Mohammed AKH. BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function. J Alzheimers Dis 2017; 55:645-657. [PMID: 27716670 PMCID: PMC6135088 DOI: 10.3233/jad-160593] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.
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Affiliation(s)
- Krister Håkansson
- Department of Psychology, Linnaeus University, Växjö, Sweden
- Center for Alzheimer Research, Division of Neurogeriatrics, Department of NVS, Karolinska Institutet, Stockholm, Sweden
- Aging Research Center (ARC), Department of NVS, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Aurélie Ledreux
- Department of Neurosciences and the Center on Aging, Medical University of South Carolina, Charleston, SC, USA
| | - Kirk Daffner
- Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Patrick Bergman
- Department of Sport Science, Linnaeus University, Växjö, Sweden
| | - Roger Carlsson
- Department of Psychology, Linnaeus University, Växjö, Sweden
| | - Miia Kivipelto
- Center for Alzheimer Research, Division of Neurogeriatrics, Department of NVS, Karolinska Institutet, Stockholm, Sweden
- Aging Research Center (ARC), Department of NVS, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Bengt Winblad
- Center for Alzheimer Research, Division of Neurogeriatrics, Department of NVS, Karolinska Institutet, Stockholm, Sweden
| | - Ann-Charlotte Granholm
- Department of Neurosciences and the Center on Aging, Medical University of South Carolina, Charleston, SC, USA
| | - Abdul Kadir H. Mohammed
- Department of Psychology, Linnaeus University, Växjö, Sweden
- Center for Alzheimer Research, Division of Neurogeriatrics, Department of NVS, Karolinska Institutet, Stockholm, Sweden
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APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study. Exp Gerontol 2016; 87:129-136. [PMID: 27864047 DOI: 10.1016/j.exger.2016.11.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 10/27/2016] [Accepted: 11/01/2016] [Indexed: 12/27/2022]
Abstract
Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of APOEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise-induced increase in VO2Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO2Max, and BDNF did not differ between ε4 carriers and non-ε4 carriers. A significant association between ε4 status and serum BDNF levels was detected. Non-ε4 carriers showed a significant increase in BDNF levels at the 6month time point while ε4 carriers did not. We believe we have identified a relationship between the ε4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no-exercise control group will be necessary to determine the scope of this association in the general population.
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40
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Siuda J, Patalong-Ogiewa M, Żmuda W, Targosz-Gajniak M, Niewiadomska E, Matuszek I, Jędrzejowska-Szypułka H, Lewin-Kowalik J, Rudzińska-Bar M. Cognitive impairment and BDNF serum levels. Neurol Neurochir Pol 2016; 51:24-32. [PMID: 28341039 DOI: 10.1016/j.pjnns.2016.10.001] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 09/29/2016] [Accepted: 10/04/2016] [Indexed: 11/29/2022]
Abstract
BACKGROUND/AIMS To investigate the alterations of brain-derived neurotrophic factor (BNDF) serum levels in subjects with different intensity of cognitive impairment and different neurodegenerative processes. MATERIAL AND METHODS Serum BDNF levels were analyzed by ELISA kit in 378 subjects: 134 Alzheimer's disease (AD) patients, 115 amnestic mild cognitive impairment (MCI) patients, and 129 controls divided into two groups: neurodegenerative control group (ND), consisting of 49 Parkinson's disease patients without any cognitive complaints, and cognitively normal control group (CN), consisting of 80 subjects without any neurological disorders. RESULTS AD patients had significantly lower (p<0.001) BDNF serum levels compared to MCI, CN and ND controls. Age and education had significant influence on BDNF serum levels regardless the diagnosis or group assignment. We have found no influence of depression on BDNF serum levels either in our group as a whole, or in each group assessed separately. We found significant correlation between BDNF serum levels and cognitive impairments. After multiple comparisons between the groups, we found that, after adjustment for confounding factors (age, gender, education, depression, cognitive impairment), BDNF serum levels were the lowest in AD group (p=0.05). CONCLUSIONS Advanced age and low educational level are associated with decreased BDNF serum levels. Decreased BDNF serum levels correspond to the severity of cognitive impairment. There is no correlation between BDNF serum levels and depressive symptoms.
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Affiliation(s)
- Joanna Siuda
- Department of Neurology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; Department of Neurology, Central University Hospital, Katowice, Poland.
| | | | - Weronika Żmuda
- Department of Neurology, Central University Hospital, Katowice, Poland
| | | | - Ewa Niewiadomska
- Department of Biostatistics, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland
| | - Iwona Matuszek
- Department of Physiology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | | | | | - Monika Rudzińska-Bar
- Department of Neurology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; Department of Neurology, Central University Hospital, Katowice, Poland
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Campos C, Rocha NBF, Lattari E, Paes F, Nardi AE, Machado S. Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors. Expert Rev Neurother 2016; 16:723-34. [PMID: 27086703 DOI: 10.1080/14737175.2016.1179582] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Age-related neurodegenerative disorders, like Alzheimer's or Parkinson's disease, are becoming a major issue to public health care. Currently, there is no effective pharmacological treatment to address cognitive impairment in these patients. Here, we aim to explore the role of exercise-induced trophic factor enhancement in the prevention or delay of cognitive decline in patients with neurodegenerative diseases. There is a significant amount of evidence from animal and human studies that links neurodegenerative related cognitive deficits with changes on brain and peripheral trophic factor levels. Several trials with elderly individuals and patients with neurodegenerative diseases report exercise induced cognitive improvements and changes on trophic factor levels including BDNF, IGF-I, among others. Further studies with healthy aging and clinical populations are needed to understand how diverse exercise interventions produce different variations in trophic factor signaling. Genetic profiles and potential confounders regarding trophic factors should also be addressed in future trials.
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Affiliation(s)
- Carlos Campos
- a Laboratory of Panic and Respiration , Institute of Psychiatry of Federal University of Rio de Janeiro (IPUB/UFRJ) , Rio de Janeiro , Brazil.,b School of Allied Health Sciences , Polytechnic Institute of Porto , Porto , Portugal
| | - Nuno Barbosa F Rocha
- b School of Allied Health Sciences , Polytechnic Institute of Porto , Porto , Portugal
| | - Eduardo Lattari
- a Laboratory of Panic and Respiration , Institute of Psychiatry of Federal University of Rio de Janeiro (IPUB/UFRJ) , Rio de Janeiro , Brazil
| | - Flávia Paes
- a Laboratory of Panic and Respiration , Institute of Psychiatry of Federal University of Rio de Janeiro (IPUB/UFRJ) , Rio de Janeiro , Brazil
| | - António E Nardi
- a Laboratory of Panic and Respiration , Institute of Psychiatry of Federal University of Rio de Janeiro (IPUB/UFRJ) , Rio de Janeiro , Brazil
| | - Sérgio Machado
- a Laboratory of Panic and Respiration , Institute of Psychiatry of Federal University of Rio de Janeiro (IPUB/UFRJ) , Rio de Janeiro , Brazil.,c Physical Activity Neuroscience Laboratory , Physical Activity Sciences Postgraduate Program - Salgado de Oliveira University (UNIVERSO) , Niterói , Brazil
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Saxena AK, Lakshman K, Sharma T, Gupta N, Banerjee BD, Singal A. Modulation of serum BDNF levels in postherpetic neuralgia following pulsed radiofrequency of intercostal nerve and pregabalin. Pain Manag 2016; 6:217-27. [DOI: 10.2217/pmt.16.3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Aim: To study the modulation of serum BDNF levels following integrated multimodal intervention in postherpetic neuralgia (PHN). Materials & methods: A randomized, double-blind controlled study was undertaken among patients of thoracic PHN where 30 patients received pregabalin with pulsed radiofrequency and 30 controls received pregabalin with sham treatment. Results: Pain intensity (visual analog scale) was reduced earlier in intervention group (15.3 ± 5.7 at the fourth week) compared with control group (16.3 ± 6.6 at the eighth week). Serum BDNF level increased with time in both the groups with overall increase more pronounced in intervention group. Conclusion: Integrated multimodal therapy using minimally invasive pulsed radiofrequency and pregabalin in PHN was effective in early pain reduction with elevated serum BDNF levels.
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Affiliation(s)
- Ashok Kumar Saxena
- Pain Clinic, Division under Department of Anaesthesiology, University College of Medical Sciences & Guru Teg Bahadur Hospital, Delhi, India
| | - Kavitha Lakshman
- Department of Anaesthesiology & Pain Relief, Kidwai Memorial Institute of Oncology, Bangalore, India
| | - Tusha Sharma
- Department of Biochemistry, University College of Medical Sciences & Guru Teg Bahadur Hospital, Delhi, India
| | - Neha Gupta
- Pain Clinic, Division under Department of Anaesthesiology, University College of Medical Sciences & Guru Teg Bahadur Hospital, Delhi, India
| | - Basu Dev Banerjee
- Department of Biochemistry, University College of Medical Sciences & Guru Teg Bahadur Hospital, Delhi, India
| | - Archana Singal
- Department of Dermatology, University College of Medical Sciences & Guru Teg Bahadur Hospital, Delhi, India
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Serra-Millàs M. Are the changes in the peripheral brain-derived neurotrophic factor levels due to platelet activation? World J Psychiatry 2016; 6:84-101. [PMID: 27014600 PMCID: PMC4804271 DOI: 10.5498/wjp.v6.i1.84] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 11/08/2015] [Accepted: 01/22/2016] [Indexed: 02/05/2023] Open
Abstract
Brain-derived neurotrophic factor (BDNF) plays an important role in central nervous system development, neurogenesis and neuronal plasticity. BDNF is also expressed in several non-neuronal tissues, and it could play an important role in other processes, such as cancer, angiogenesis, etc. Platelets are the major source of peripheral BDNF. However, platelets also contain high amounts of serotonin; they express specific surface receptors during activation, and a multitude of pro-inflammatory and immunomodulatory bioactive compounds are secreted from the granules. Until recently, there was insufficient knowledge regarding the relationship between BDNF and platelets. Recent studies showed that BDNF is present in two distinct pools in platelets, in α-granules and in the cytoplasm, and only the BDNF in the granules is secreted following stimulation, representing 30% of the total BDNF in platelets. BDNF has an important role in the pathophysiology of depression. Low levels of serum BDNF have been described in patients with major depressive disorder, and BDNF levels increased with chronic antidepressant treatment. Interestingly, there is an association between depression and platelet function. This review analyzed studies that evaluated the relationship between BDNF and platelet activation and the effect of treatments on both parameters. Only a few studies consider this possible confounding factor, and it could be very important in diseases such as depression, which show changes in both parameters.
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Gomazkov OA. [Signaling molecules in the brain and epigenetic factors in neurodegenerative and mental disorders]. Zh Nevrol Psikhiatr Im S S Korsakova 2015; 115:102-110. [PMID: 26649375 DOI: 10.17116/jnevro2015115101102-110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The literature on a role of signaling molecules in the organization of memory and cognitive functions is analyzed basing on mechanisms of memory physiology determined by a complex of biochemical processes initiated by the transmission of the signal to the synapse and completed by the synthesis of functionally significant molecules in the neuronal genetic apparatus. The center of these processes is a coordinated system of signal transduction, transcription, epigenetic and neurotrophic molecules. The dissonance of signal mechanisms is a prime cause of memory impairment and cognitive dysfunction as social maladaptation factors. The results of experimental and clinical studies of a role of the multilevel signaling system in age-related, neurodegenerative (Alzheimer’s disease) and mental (depression) disorders are discussed. At the same time, signaling molecules may be considered as particular targets for new therapeutic approaches.
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Affiliation(s)
- O A Gomazkov
- Orekhovich Research Institute of Biomedical Chemistry, Moscow
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45
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Differential role of estrogen receptor modulators in depression-like behavior and memory impairment in rats with postmenopausal diabetes. Menopause 2015; 22:1117-24. [DOI: 10.1097/gme.0000000000000435] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression. J Neuroimmunol 2015; 287:88-92. [DOI: 10.1016/j.jneuroim.2015.08.012] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2015] [Revised: 08/10/2015] [Accepted: 08/19/2015] [Indexed: 11/22/2022]
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Failla MD, Juengst SB, Arenth PM, Wagner AK. Preliminary Associations Between Brain-Derived Neurotrophic Factor, Memory Impairment, Functional Cognition, and Depressive Symptoms Following Severe TBI. Neurorehabil Neural Repair 2015; 30:419-30. [PMID: 26276123 DOI: 10.1177/1545968315600525] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
UNLABELLED Background Traumatic brain injury (TBI) often leads to mood and cognitive complications, affecting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective To evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods Participants with TBI (n = 113) were evaluated for PTD (Patient Health Questionnaire-9 [PHQ-9]), cognitive impairment (cognitive composite score), and functional cognition (Functional Independence Measure-Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid and serum at 0 to 6 days postinjury and in serum at 6 and 12 months postinjury. RESULTS Serum BDNF was reduced after TBI versus controls at all time points. Acute serum BDNF positively correlated with memory composites (6 months: r = 0.43, P = .019, n = 30; 12 months: r = 0.53, P = .005, n = 26) and FIM-Memory scores (6 months: r = 0.35, P = .019, n = 45; 12 months: r = 0.38, P = .018, n = 38). Acute serum BDNF negatively correlated with 12-month PHQ-9 scores (r = -0.38; P = .044; n = 29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (P = .07) and correlated with PHQ-9 scores (r = -0.41; P = .019; n = 32). Conclusions Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI.
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Affiliation(s)
- Michelle D Failla
- Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
| | - Shannon B Juengst
- Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Patricia M Arenth
- Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Amy K Wagner
- Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Vinberg M, Miskowiak K, Hoejman P, Pedersen M, Kessing LV. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study. PLoS One 2015; 10:e0127629. [PMID: 26011424 PMCID: PMC4444304 DOI: 10.1371/journal.pone.0127629] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 04/16/2015] [Indexed: 02/01/2023] Open
Abstract
The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU) or saline (0.9% NaCl) infusions in a double-blind, placebo-controlled, parallel—group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95% CI): EPO 10.94 ng/l (4.51-21.41 ng/l); mean increase at week 9: Saline 0.52 ng/l, p=0.04 (-5.88-4.48 ng/l) p=0.04, partial ŋ2=0.12). No significant effects were found on BDNF levels in partially remitted patients with BD (p=0.35). The present effects of EPO on BDNF levels in patients with TRD point to a role of neurotrophic factors in the potential effects of EPO seen in TRD and BD. The neurobiological mechanisms underlying these effects and the interaction between EPO and peripheral levels on BDNF need to be further elucidated in human studies including a broad range of biomarkers.
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Affiliation(s)
- Maj Vinberg
- Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen Blegdamsvej 9, DK-2100 Copenhagen, Denmark
- * E-mail:
| | - Kamilla Miskowiak
- Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Pernille Hoejman
- Centre of Inflammation and Metabolism and Centre of Physical Activity Research, Rigshospitalet, 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Maria Pedersen
- Centre of Inflammation and Metabolism and Centre of Physical Activity Research, Rigshospitalet, 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Lars Vedel Kessing
- Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen Blegdamsvej 9, DK-2100 Copenhagen, Denmark
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Protective Effects of BDNF against C-Reactive Protein-Induced Inflammation in Women. Mediators Inflamm 2015; 2015:516783. [PMID: 26161003 PMCID: PMC4460236 DOI: 10.1155/2015/516783] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Revised: 05/11/2015] [Accepted: 05/14/2015] [Indexed: 11/28/2022] Open
Abstract
Background. Since high sensitivity C-reactive protein (hsCRP) is predictive of cardiovascular events, it is important to examine the relationship between hsCRP and other inflammatory and oxidative stress markers linked to cardiovascular disease (CVD) etiology. Previously, we reported that hsCRP induces the oxidative stress adduct 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodG) and that these markers are significantly associated in women. Recent data indicates that brain-derived neurotrophic factor (BDNF) may have a role in CVD. Methods and Results. We examined BDNF levels in 3 groups of women that were age- and race-matched with low (<3 mg/L), mid (>3–20 mg/L), and high (>20 mg/L) hsCRP (n = 39 per group) and found a significant association between hsCRP, BDNF, and 8-oxodG. In African American females with high hsCRP, increases in BDNF were associated with decreased serum 8-oxodG. This was not the case in white women where high hsCRP was associated with high levels of BDNF and high levels of 8-oxodG. BDNF treatment of cells reduced CRP levels and inhibited CRP-induced DNA damage. Conclusion. We discovered an important relationship between hsCRP, 8-oxodG, and BDNF in women at hsCRP levels >3 mg/L. These data suggest that BDNF may have a protective role in counteracting the inflammatory effects of hsCRP.
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Failla MD, Conley YP, Wagner AK. Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related Mortality: Interrelationships Between Genetics and Acute Systemic and Central Nervous System BDNF Profiles. Neurorehabil Neural Repair 2015; 30:83-93. [PMID: 25979196 DOI: 10.1177/1545968315586465] [Citation(s) in RCA: 82] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Older adults have higher mortality rates after severe traumatic brain injury (TBI) compared to younger adults. Brain-derived neurotrophic factor (BDNF) signaling is altered in aging and is important to TBI given its role in neuronal survival/plasticity and autonomic function. Following experimental TBI, acute BDNF administration has not been efficacious. Clinically, genetic variation in BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) can be protective against acute mortality. Postacutely, these genotypes carry lower mortality risk in older adults and greater mortality risk among younger adults. OBJECTIVE Investigate BDNF levels in mortality/outcome following severe TBI in the context of age and genetic risk. METHODS Cerebrospinal fluid (CSF) and serum BDNF were assessed prospectively during the first week following severe TBI (n = 203) and in controls (n = 10). Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors. RESULTS CSF BDNF levels tended to be higher post-TBI (P = .061) versus controls and were associated with time until death (P = .042). In contrast, serum BDNF levels were reduced post-TBI versus controls (P < .0001). Both gene * BDNF serum and gene * age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI (P = .07). CONCLUSIONS BDNF levels predicted mortality, in addition to gene * age interactions, suggesting levels capture additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to injury and age-related increases in pro-apoptotic BDNF target receptors. Negative CSF and serum BDNF correlations post-TBI suggest blood-brain barrier transit alterations. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment.
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Affiliation(s)
- Michelle D Failla
- Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
| | - Yvette P Conley
- Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Health Promotion & Development, School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Amy K Wagner
- Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA Department of Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA
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