|
1
|
Lu J, Mao H, Tan Y, Luo G. Associations of Dietary Intake of Vitamin B6 and Plasma Pyridoxal 5'-Phosphate Level With Depression in US Adults: Findings From NHANES 2005-2010. Brain Behav 2024; 14:e70128. [PMID: 39508477 PMCID: PMC11541856 DOI: 10.1002/brb3.70128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 09/20/2024] [Accepted: 10/18/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Evidence regarding the associations of pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk is scarce. Accordingly, we investigated the aforementioned associations in US adults. METHODS This is a cross-sectional study that included data from two independent samples of 12,716 and 11,967 individuals (aged ≥ 20 years) participating in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The associations of the pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk were examined through multivariable logistic regression. In addition, we determined dose-response associations by fitting restricted cubic splines to the data. RESULTS In the multivariable model, the highest quarter of dietary intake of vitamin B6 was associated with a significantly lower risk of depression compared to the lowest quarter (OR = 0.63, 95% CI: 0.50, 0.79, p < 0.001). Similarly, the highest quartile of plasma PLP levels was linked to a reduced risk of depression compared to the lowest quartile (OR = 0.76, 95% CI: 0.62, 0.93, p < 0.01). With increasing quartiles of dietary intake of vitamin B6 and plasma PLP levels, the risk of depression also decreased accordingly (all p for trend < 0.01). Furthermore, the correlation analysis revealed that for every 1-SD increase in the level of plasma lutein + zeaxanthin and dietary intake of vitamin B6, the risk of depression showed a decreasing trend (all p < 0.01). The interaction test results indicated that the dietary consumption of vitamin B6 did not significantly interact with any of the stratification factors (all p for interaction > 0.05). Moreover, no significant interaction was found between the amount of plasma PLP and any hierarchical factors (all p for interaction > 0.05), except for gender-based subgroup analysis (p for interaction > 0.05). The dose-response relationship results showed a linear decrease trend in the relationship between dietary vitamin B6 intake and plasma pyridoxal 5'-phosphate with the risk of depression. CONCLUSIONS Plasma PLP levels and dietary vitamin B6 intake in the highest quartiles are associated with a lower risk of depression. These findings support the promotion of a balanced diet rich in vitamin B6. However, future randomized controlled trials are necessary to confirm the effects of vitamin B6 supplementation on depression risk. We should aim for a healthy and balanced diet in terms of nutritional supplementation.
Collapse
Affiliation(s)
- Jinhong Lu
- Department of General SurgeryZhujiang Hospital, Southern Medical UniversityGuangzhouChina
| | - Huina Mao
- Nursing DepartmentZhujiang Hospital, Southern Medical UniversityGuangzhouChina
| | - Yulei Tan
- Department of General SurgeryZhujiang Hospital, Southern Medical UniversityGuangzhouChina
| | - Guizhi Luo
- Department of General SurgeryZhujiang Hospital, Southern Medical UniversityGuangzhouChina
| |
Collapse
|
|
2
|
Tappia PS, Shah AK, Dhalla NS. The Efficacy of Vitamins in the Prevention and Treatment of Cardiovascular Disease. Int J Mol Sci 2024; 25:9761. [PMID: 39337248 PMCID: PMC11432297 DOI: 10.3390/ijms25189761] [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: 08/09/2024] [Revised: 09/04/2024] [Accepted: 09/06/2024] [Indexed: 09/30/2024] Open
Abstract
Vitamins are known to affect the regulation of several biochemical and metabolic pathways that influence cellular function. Adequate amounts of both hydrophilic and lipophilic vitamins are required for maintaining normal cardiac and vascular function, but their deficiencies can contribute to cardiovascular abnormalities. In this regard, a deficiency in the lipophilic vitamins, such as vitamins A, D, and E, as well as in the hydrophilic vitamins, such as vitamin C and B, has been associated with suboptimal cardiovascular function, whereas additional intakes have been suggested to reduce the risk of atherosclerosis, hypertension, ischemic heart disease, arrhythmias, and heart failure. Here, we have attempted to describe the association between low vitamin status and cardiovascular disease, and to offer a discussion on the efficacy of vitamins. While there are inconsistencies in the impact of a deficiency in vitamins on the development of cardiovascular disease and the benefits associated with supplementation, this review proposes that specific vitamins may contribute to the prevention of cardiovascular disease in individuals at risk rather than serve as an adjunct therapy.
Collapse
Affiliation(s)
- Paramjit S Tappia
- Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
| | - Anureet K Shah
- Department of Nutrition and Food Science, California State University Los Angeles, Los Angeles, CA 90032, USA
| | - Naranjan S Dhalla
- Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada
- Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2E 0J9, Canada
| |
Collapse
|
|
3
|
Dhar I, Svingen GF, Bjørnestad EØ, Ulvik A, Saeed S, Nygård OK. B-vitamin treatment modifies the mortality risk associated with calcium channel blockers in patients with suspected stable angina pectoris: A prospective cohort study. Am J Clin Nutr 2023:S0002-9165(23)48891-0. [PMID: 37121550 PMCID: PMC10375456 DOI: 10.1016/j.ajcnut.2023.04.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 04/04/2023] [Accepted: 04/27/2023] [Indexed: 05/02/2023] Open
Abstract
BACKGROUND Calcium channel blockers (CCBs) are used for the treatment of cardiovascular disease (CVD), including angina pectoris, and hypertension; however, the effect on survival remains uncertain. CCBs impair fibrinolysis and have been linked to elevated plasma homocysteine (Hcy), a CVD risk marker. OBJECTIVE We explored the association between CCB use and mortality in a large prospective cohort of patients with suspected stable angina pectoris (SAP), and potential effect modifications by Hcy-lowering B-vitamin treatment (folic acid, B12 and/or B6) as 61.8% of the patients participated in a randomized placebo-controlled B-vitamin intervention trial. METHODS Patient baseline continuous characteristics according to CCB treatment were tested by linear regression. Hazard ratios (HRs) for mortality associated with CCB treatment, also according to B-vitamin intervention, were examined using Cox regression analysis. The multivariable model included cardiovascular risk factors, medical histories, and use of CVD medications. RESULTS A total of 3991 patients (71.5 % men) were included, of whom 907 were prescribed CCBs at discharge. During 10.3 years of median follow-up, 20.6% died and 8.9% from cardiovascular- and 11.6% from non-cardiovascular causes. Patients treated with CCBs had higher plasma Hcy, fibrinogen levels and erythrocyte sedimentation rate (all P<0.001). Further, CCB use was positively associated with mortality, also after multivariable adjustments (HRs [95% CIs]: 1.34 [1.15-1.57], 1.35 [1.08-1.70] and 1.33 [1.09-1.64] for total, CVD and non-CVD death, respectively). Numerically stronger associations were observed among patients not treated with B-vitamins (HR [95% CI]: 1.54 [1.25-1.88], 1.69 [1.25-2.30] and 1.41 [1.06- 1.86] for total, CVD and non-CVD death, respectively), whereas, no association was seen in patients treated with B-vitamins (HR [95% CI]: 1.15 [0.91-1.46], 1.09 [0.76-1.57] and 1.20 [0.88-1.65]). CONCLUSIONS In patients with suspected SAP, CCB treatment was associated with increased mortality risk primarily among patients not treated with B-vitamins. CLINICAL TRIAL REGISTRATION-URL https://clinicaltrials.gov/ct2/show/NCT00354081?term=NCT00354081&draw=2&rank=1. Clinical Trial Registration-Unique identifier (NCT number): NCT00354081.
Collapse
Affiliation(s)
- Indu Dhar
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway; Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Norway.
| | - Gard Ft Svingen
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Espen Ø Bjørnestad
- Department of Cardiology, Stavanger University Hospital, Stavanger, Norway
| | | | - Sahrai Saeed
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Ottar K Nygård
- Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway; Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| |
Collapse
|
|
4
|
Mistry J, Biswas M, Sarkar S, Ghosh S. Antidiabetic activity of mango peel extract and mangiferin in alloxan-induced diabetic rats. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2023. [DOI: 10.1186/s43094-023-00472-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2023] Open
Abstract
Abstract
Background
In diabetic animals, there is a significant increase in plasma glucose, serum total cholesterol, triglyceride, and low-density lipoprotein levels, and decreased body weight, liver and muscle glycogen, and high-density lipoprotein. Effective treatment of diabetes mellitus is not yet known, even though the management of diabetes mellitus is considered a global concern. Plants and herbs have played an important role in the healthcare of many societies throughout history. Today’s researchers are investigating the potential for using these nonpharmaceutical approaches to treat and control diabetes, either in conjunction with standard treatments or as an alternative to them. Herbal formulations are favored because to lower cost and fewer side effects compared to other methods for alleviating diabetes and its consequences. In ethnomedicinal practices, different parts of Mangifera indica are used to treatment of diabetes. The present investigation was undertaken to evaluate the antidiabetic activity of an ethanolic extract of Mangifera indica and mangiferin in alloxan-induced diabetic rats. This experiment was conducted in a set of two with four groups of animals namely control (Tc), treatment alloxan (Ta), treatment extract (Tae), and treatment mangiferin (Tam). To develop diabetes, Wistar rats treated with 150 mg/kg b.w. of alloxan monohydrate were injected intraperitoneally. Tae and Tam’s groups received a freshly prepared single dose of extract and mangiferin in distilled water via the oral route. All experimental groups received laboratory pallet feed diet and drinking water ad libitum. Diabetic rats were treated for 21 days with an ethanolic extract of mango peel and pure mangiferin orally daily at rates of 200 mg/kg b.w. and 20 mg/kg b.w.
Results
An alloxan-induced diabetic rat treated with mango peel extract and mangiferin significantly improved the overhead impact due to diabetes. There was a significant (p < 0.05) body weight loss in the alloxan-induced diabetic rats (Ta), whereas animals given mango peel extract and mangiferin showed a significant increase in body weight from 2 weeks onwards in comparison with control. Alloxan-induced rats (Ta) group have higher blood glucose levels and are significantly different (p < 0.01) from the control group. Mango peel extract and mangiferin significantly reduced the levels of fasting glucose after 21 days of treatment in comparison with diabetic animals. Mango peel extract and mangiferin influence the glycogen synthesis pathway in diabetes groups by increasing glycogen levels in muscle and liver. mango peel extract and mangiferin were found to have a nonsignificant impact on plasma cholesterol and HDL levels compared with the control group. Mango peel extract was found to have a significant difference (p < 0.05) in LDL levels compared with the control group. Mangiferin was found to have a significant difference (p < 0.05) in triglyceride and VLDL levels when compared with the control group. Histopathological examination of the pancreas in rats with type I diabetes caused by alloxan found that therapy with an ethanolic extract of mango peel and mangiferin restored beta cell function as well as rejuvenation of Islets of Langerhans.
Conclusions
Mango peel extract and mangiferin have antidiabetic, glycogenesis, and hypolipidemic properties when administered to alloxan-induced diabetic rats.
Graphical abstract
Collapse
|
|
5
|
Paez-Hurtado AM, Calderon-Ospina CA, Nava-Mesa MO. Mechanisms of action of vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) in pain: a narrative review. Nutr Neurosci 2023; 26:235-253. [PMID: 35156556 DOI: 10.1080/1028415x.2022.2034242] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Pain is a complex sensory and emotional experience with nociceptive, nociplastic, and neuropathic components. An involvement of neurotropic B vitamins (B1 - thiamine, B6 - pyridoxine, and B12 - cyanocobalamin) as modulators of inflammation and pain has been long discussed. New evidence suggests their therapeutic potential in different pain conditions. In this review, we discuss the main role of neurotropic B vitamins on different nociceptive pathways in the nervous system and to describe their analgesic action mechanisms. The performed literature review showed that, through different mechanisms, these vitamins regulate several inflammatory and neural mediators in nociceptive and neuropathic pain. Some of these processes include aiming the activation of the descending pain modulatory system and in specific intracellular pathways, anti-inflammatory, antioxidative and nerve regenerative effects. Moreover, recent data shows the antinociceptive, antiallodynic, and anti-hyperalgesic effects of the combination of these vitamins, as well as their synergistic effects with known analgesics. Understanding how vitamins B1, B6, and B12 affect several nociceptive mechanisms can therefore be of significance in the treatment of various pain conditions.
Collapse
Affiliation(s)
- A M Paez-Hurtado
- Neuroscience Research Group (NEUROS)-Centro Neurovitae, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - C A Calderon-Ospina
- Center for Research in Genetics and Genomics (CIGGUR), GENIUROS Research Group, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - M O Nava-Mesa
- Neuroscience Research Group (NEUROS)-Centro Neurovitae, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| |
Collapse
|
|
6
|
Lu W, Wang Y, Fang Z, Wang H, Zhu J, Zhai Q, Zhao J, Zhang H, Chen W. Bifidobacterium longum CCFM752 prevented hypertension and aortic lesion, improved antioxidative ability, and regulated the gut microbiome in spontaneously hypertensive rats. Food Funct 2022; 13:6373-6386. [PMID: 35615892 DOI: 10.1039/d1fo04446j] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Oxidative stress and gut dysbiosis are important risk factors for hypertension. In this study, the preventive effect of Bifidobacterium longum CCFM752 (CCFM752) on hypertension was evaluated. 5-week-old spontaneously hypertensive rats (SHR) were treated with vehicle or CCFM752 (1.0 × 109 CFU day-1) for 12 weeks. The increase in systolic blood pressure and diastolic blood pressure was significantly prevented by CCFM752 treatment. Simultaneously, CCFM752 prevented aortic fibrosis and hypertrophy and increased aortic endothelial nitric oxide synthase (eNOS) activity. CCFM752 presented an antioxidative effect by inhibiting aortic NADPH oxidase activation and increasing aortic and serum catalase activity, and reducing aortic reactive oxygen species (ROS). The gut dysbiosis of SHR, including the increased Firmicutes/Bacteroidetes ratio, decreased Actinobacteria as well as reduced α-diversity, were restored by CCFM752. CCFM752 also increased the prevalence of Bifidobacterium and Lactobacillus, while decreasing Turicibacter at the genus level. Furthermore, serum metabolomic analysis revealed that CCFM752 up-regulated serum proline and pyridoxamine 5'-phosphate, both of which were negatively correlated with blood pressure. In conclusion, the positive impact of CCFM752 on the gut microbiota may contribute to the antioxidative effect as well as its preventive effect on hypertension.
Collapse
Affiliation(s)
- Wenwei Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, PR China
| | - Yusheng Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China
| | - Zhifeng Fang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China
| | - Hongchao Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China
| | - Jinlin Zhu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, PR China.,Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi 214122, PR China.,(Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, PR China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China. .,School of Food Science and Technology, Jiangnan University, Wuxi 214122, PR China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, PR China
| |
Collapse
|
|
7
|
Shah AK, Dhalla NS. Effectiveness of Some Vitamins in the Prevention of Cardiovascular Disease: A Narrative Review. Front Physiol 2021; 12:729255. [PMID: 34690803 PMCID: PMC8531219 DOI: 10.3389/fphys.2021.729255] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 09/17/2021] [Indexed: 01/01/2023] Open
Abstract
By virtue of their regulatory role in various metabolic and biosynthetic pathways for energy status and cellular integrity, both hydro-soluble and lipo-soluble vitamins are considered to be involved in maintaining cardiovascular function in health and disease. Deficiency of some vitamins such as vitamin A, B6, folic acid, C, D, and E has been shown to be associated with cardiovascular abnormalities whereas supplementation with these vitamins has been claimed to reduce cardiovascular risk for hypertension, atherosclerosis, myocardial ischemia, arrhythmias, and heart failure. However, the data from several experimental and clinical studies for the pathogenesis of cardiovascular disease due to vitamin deficiency as well as therapy due to different vitamins are conflicting. In this article, we have attempted to review the existing literature on the role of different vitamins in cardiovascular disease with respect to their deficiency and supplementation in addition to examining some issues regarding their involvement in heart disease. Although both epidemiological and observational studies have shown some merit in the use of different antioxidant vitamins for the treatment of cardiovascular disorders, the results are not conclusive. Furthermore, in view of the complexities in the mechanisms of different cardiovascular disorders, no apparent involvement of any particular vitamin was seen in any specific cardiovascular disease. On the other hand, we have reviewed the evidence that deficiency of vitamin B6 promoted KCl-induced Ca2+ entry and reduced ATP-induced Ca2+-entry in cardiomyocytes in addition to decreasing sarcolemmal (SL) ATP binding. The active metabolite of vitamin B6, pyridoxal 5′-phosphate, attenuated arrhythmias due to myocardial infarction (MI) as well as cardiac dysfunction and defects in the sarcoplasmic reticulum (SR) Ca2+-transport in the ischemic-reperfused hearts. These observations indicate that both deficiency of some vitamins as well as pretreatments with different vitamins showing antioxidant activity affect cardiac function, metabolism and cation transport, and support the view that antioxidant vitamins or their metabolites may be involved in the prevention rather than the therapy of cardiovascular disease.
Collapse
Affiliation(s)
- Anureet K Shah
- School of Kinesiology, Nutrition and Food Science, California State University, Los Angeles, Los Angeles, CA, United States
| | - Naranjan S Dhalla
- Department of Physiology and Pathophysiology, St. Boniface Hospital Albrechtsen Research Centre, Max Rady College of Medicine, Institute of Cardiovascular Sciences, University of Manitoba, Winnipeg, MB, Canada
| |
Collapse
|
|
8
|
Al-Shekaili HH, Petkau TL, Pena I, Lengyell TC, Verhoeven-Duif NM, Ciapaite J, Bosma M, van Faassen M, Kema IP, Horvath G, Ross C, Simpson EM, Friedman JM, van Karnebeek C, Leavitt BR. A novel mouse model for pyridoxine-dependent epilepsy due to antiquitin deficiency. Hum Mol Genet 2021; 29:3266-3284. [PMID: 32969477 DOI: 10.1093/hmg/ddaa202] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 08/18/2020] [Accepted: 08/27/2020] [Indexed: 01/09/2023] Open
Abstract
Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disease caused by mutations in the ALDH7A1 gene leading to blockade of the lysine catabolism pathway. PDE is characterized by recurrent seizures that are resistant to conventional anticonvulsant treatment but are well-controlled by pyridoxine (PN). Most PDE patients also suffer from neurodevelopmental deficits despite adequate seizure control with PN. To investigate potential pathophysiological mechanisms associated with ALDH7A1 deficiency, we generated a transgenic mouse strain with constitutive genetic ablation of Aldh7a1. We undertook extensive biochemical characterization of Aldh7a1-KO mice consuming a low lysine/high PN diet. Results showed that KO mice accumulated high concentrations of upstream lysine metabolites including ∆1-piperideine-6-carboxylic acid (P6C), α-aminoadipic semialdehyde (α-AASA) and pipecolic acid both in brain and liver tissues, similar to the biochemical picture in ALDH7A1-deficient patients. We also observed preliminary evidence of a widely deranged amino acid profile and increased levels of methionine sulfoxide, an oxidative stress biomarker, in the brains of KO mice, suggesting that increased oxidative stress may be a novel pathobiochemical mechanism in ALDH7A1 deficiency. KO mice lacked epileptic seizures when fed a low lysine/high PN diet. Switching mice to a high lysine/low PN diet led to vigorous seizures and a quick death in KO mice. Treatment with PN controlled seizures and improved survival of high-lysine/low PN fed KO mice. This study expands the spectrum of biochemical abnormalities that may be associated with ALDH7A1 deficiency and provides a proof-of-concept for the utility of the model to study PDE pathophysiology and to test new therapeutics.
Collapse
Affiliation(s)
- Hilal H Al-Shekaili
- British Columbia Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| | - Terri L Petkau
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| | - Izabella Pena
- Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
| | - Tess C Lengyell
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| | | | - Jolita Ciapaite
- Department of Genetics, University Medical Center, Utrecht, The Netherlands
| | - Marjolein Bosma
- Department of Genetics, University Medical Center, Utrecht, The Netherlands
| | - Martijn van Faassen
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ido P Kema
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Gabriella Horvath
- Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, BC, Canada
| | - Colin Ross
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
| | - Elizabeth M Simpson
- British Columbia Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.,Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| | - Jan M Friedman
- British Columbia Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.,Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| | - Clara van Karnebeek
- Department of Pediatrics, Centre for Molecular Medicine and Therapeutics, BC Children's Research Institute, University of British Columbia, Vancouver, BC, Canada.,Department of Pediatrics, Emma Children's Hospital, Amsterdam University Medical Centres, Amsterdam, The Netherlands.,Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Blair R Leavitt
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| |
Collapse
|
|
9
|
Stephen DSS, Abraham A. High-fat simple carbohydrate (HFSC) diet impairs hypothalamic and corpus striatal serotonergic metabolic pathway in metabolic syndrome (MetS) induced C57BL/6J mice. Nutr Neurosci 2017; 22:51-62. [DOI: 10.1080/1028415x.2017.1354511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- DSouza Serena Stephen
- Father George Albuquerque Pai Cell and Molecular Biology Laboratory, Department of Postgraduate Studies and Research in Biotechnology, St Aloysius (Autonomous) College, Mangaluru 575003, Karnataka, India
- 125-B, Protein Engineering Laboratory, Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
| | - Asha Abraham
- Father George Albuquerque Pai Cell and Molecular Biology Laboratory, Department of Postgraduate Studies and Research in Biotechnology, St Aloysius (Autonomous) College, Mangaluru 575003, Karnataka, India
| |
Collapse
|
|
10
|
Dakshinamurti S, Dakshinamurti K. Antihypertensive and neuroprotective actions of pyridoxine and its derivatives. Can J Physiol Pharmacol 2015; 93:1083-90. [PMID: 26281007 DOI: 10.1139/cjpp-2015-0098] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Vitamin B6 plays a crucial role in the nervous system as the amino acid decarboxylases involved in the synthesis of all putative neurotransmitters requires the coenzyme pyridoxal phosphate. Vitamin B6 in its various forms has antioxidant properties. Pyridoxal phosphate has a role in regulating cellular calcium transport through both the voltage-mediated and ATP-mediated purinergic mechanisms of cellular calcium influx and, hence, has a role in the control of hypertension. Pharmacological doses of vitamin B6 appear to decrease the high blood pressure associated with both genetic and nongenetic models of hypertension. Vitamin B6 has a crucial role in the normal function of the central and peripheral nervous systems. It also protects against ischemia and glutamate-induced neurotoxicity.
Collapse
Affiliation(s)
- Shyamala Dakshinamurti
- a Departments of Pediatrics and Physiology, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Krishnamurti Dakshinamurti
- b St. Boniface Hospital Research Centre, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| |
Collapse
|
|
11
|
Houston M. The role of nutrition and nutraceutical supplements in the treatment of hypertension. World J Cardiol 2014; 6:38-66. [PMID: 24575172 PMCID: PMC3935060 DOI: 10.4330/wjc.v6.i2.38] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 10/22/2013] [Accepted: 12/17/2013] [Indexed: 02/06/2023] Open
Abstract
Vascular biology, endothelial and vascular smooth muscle and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients can prevent, control and treat hypertension through numerous mechanisms related to vascular biology. Oxidative stress, inflammation and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the selected use of single and component nutraceutical supplements, vitamins, antioxidants and minerals in the treatment of hypertension based on scientifically controlled studies which complement optimal nutrition, coupled with other lifestyle modifications.
Collapse
Affiliation(s)
- Mark Houston
- Mark Houston, Hypertension Institute, Saint Thomas Medical Plaza, Nashville, TN 37205, United States
| |
Collapse
|
|
12
|
George AK, Paul J, Kaimal SB, Paulose CS. Decreased cerebral cortex and liver 5-HT2Areceptor gene expression and enhanced ALDH activity in ethanol-treated rats and hepatocyte cultures. Neurol Res 2013; 32:510-8. [DOI: 10.1179/174313209x385554] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
|
|
13
|
Houston M. Nutrition and nutraceutical supplements for the treatment of hypertension: part III. J Clin Hypertens (Greenwich) 2013; 15:931-7. [PMID: 24119210 PMCID: PMC8033946 DOI: 10.1111/jch.12211] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Revised: 08/26/2013] [Accepted: 08/28/2013] [Indexed: 02/05/2023]
Abstract
Vascular biology, endothelial and vascular smooth muscle, and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease, and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients can prevent, control, and treat hypertension through numerous mechanisms related to vascular biology. Oxidative stress, inflammation, and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the selected use of single and component nutraceutical supplements, vitamins, antioxidants, and minerals in the treatment of hypertension based on scientifically controlled studies that complement optimal nutrition, coupled with other lifestyle modifications.
Collapse
Affiliation(s)
- Mark Houston
- Department of MedicineVanderbilt University School of MedicineHypertension Institute of NashvilleSaint Thomas Medical Group and Health ServicesSaint Thomas HospitalNashvilleTN
| |
Collapse
|
|
14
|
Houston MC. The role of nutrition and nutraceutical supplements in the prevention and treatment of hypertension. ACTA ACUST UNITED AC 2013. [DOI: 10.2217/cpr.13.2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
|
|
15
|
Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease. Clin Chem Lab Med 2013; 51:535-43. [DOI: 10.1515/cclm-2012-0553] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Accepted: 11/09/2012] [Indexed: 11/15/2022]
|
|
16
|
Nandhu MS, Paul J, Kuruvilla KP, Malat A, Romeo C, Paulose CS. Enhanced glutamate, IP3 and cAMP activity in the cerebral cortex of unilateral 6-hydroxydopamine induced Parkinson's rats: effect of 5-HT, GABA and bone marrow cell supplementation. J Biomed Sci 2011; 18:5. [PMID: 21235809 PMCID: PMC3027092 DOI: 10.1186/1423-0127-18-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2010] [Accepted: 01/15/2011] [Indexed: 12/29/2022] Open
Abstract
Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in Bmax (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B, mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's disease is of prominence.
Collapse
Affiliation(s)
- M S Nandhu
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin - 682 022, and Kerala, India
| | | | | | | | | | | |
Collapse
|
|
17
|
Abraham PM, Kuruvilla KP, Mathew J, Malat A, Joy S, Paulose CS. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose. J Biomed Sci 2010; 17:78. [PMID: 20868513 PMCID: PMC2955644 DOI: 10.1186/1423-0127-17-78] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Accepted: 09/25/2010] [Indexed: 01/23/2023] Open
Abstract
Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters Bmax and Kd showed a significant decrease (p < 0.001) whereas 5-HT2A receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.
Collapse
Affiliation(s)
- Pretty Mary Abraham
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin- 682 022, Kerala, India
| | | | | | | | | | | |
Collapse
|
|
18
|
Abraham PM, Anju TR, Jayanarayanan S, Paulose CS. Serotonergic receptor upregulation in cerebral cortex and down regulation in brainstem of streptozotocin induced diabetic rats: antagonism by pyridoxine and insulin. Neurosci Lett 2010; 483:23-7. [PMID: 20655360 DOI: 10.1016/j.neulet.2010.07.042] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2010] [Revised: 07/13/2010] [Accepted: 07/16/2010] [Indexed: 12/31/2022]
Abstract
Insulin secretion and glucose homeostasis is implicated through serotonergic function. Pyridoxine is involved in decarboxylation step in synthesis of serotonin. The present study was carried out to find the role of insulin in combination with pyridoxine on the concentrations of 5-HT and 5-HIAA, 5-HT receptor binding, 5-HTT gene expression and immunohistochemistry studies in the cerebral cortex and brainstem of streptozotocin induced diabetic rats. 5-HT content showed a significant decrease with a significant increase in 5-HIAA in cerebral cortex (p<0.01) and brain stem (p<0.001) in diabetic rats. 5-HT receptor binding parameters, B(max) and K(d), showed a significant decrease (p<0.001) in diabetic rats in cerebral cortex whereas in brainstem it showed a significant increase (p<0.001) compared to control. Gene expression studies of 5-HTT in cerebral cortex showed a significant down regulation (p<0.001) and in brainstem an upregulation (p<0.001) in diabetic rats compared to control. Insulin and pyridoxine treatment to diabetic rats reversed the 5-HT content, B(max), K(d) and gene expression of 5-HTT confirmed by immunohistochemistry studies in cerebral cortex and brainstem to near control. Thus our results suggest that pyridoxine along with insulin has a role in the regulation of insulin synthesis and release through serotonergic function which has clinical significance in the management of diabetes.
Collapse
Affiliation(s)
- Pretty Mary Abraham
- Molecular Neurobiology and Cell Biology Unit, Department of Biotechnology, Centre for Neuroscience, Cochin University of Science and Technology, Cochin 682 022, Kerala, India
| | | | | | | |
Collapse
|
|
19
|
Down regulation of cerebellar serotonergic receptors in streptozotocin induced diabetic rats: Effect of pyridoxine and Aegle marmelose. Brain Res Bull 2010; 82:87-94. [DOI: 10.1016/j.brainresbull.2010.02.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2009] [Revised: 02/02/2010] [Accepted: 02/10/2010] [Indexed: 11/24/2022]
|
|
20
|
Cholinergic, dopaminergic and insulin receptors gene expression in the cerebellum of streptozotocin-induced diabetic rats: Functional regulation with Vitamin D3 supplementation. Pharmacol Biochem Behav 2010; 95:216-22. [DOI: 10.1016/j.pbb.2010.01.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2009] [Revised: 01/09/2010] [Accepted: 01/18/2010] [Indexed: 01/08/2023]
|
|
21
|
Mathew J, Paul J, Nandhu MS, Paulose CS. Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri. Fitoterapia 2010; 81:546-51. [PMID: 20117182 DOI: 10.1016/j.fitote.2010.01.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2009] [Revised: 01/12/2010] [Accepted: 01/18/2010] [Indexed: 01/30/2023]
Abstract
We have evaluated the acetylcholine esterase and malate dehydrogenase activity in the muscle, epinephrine, norepinephrine, insulin and T3 content in the serum of epileptic rats. Acetylcholine esterase and malate dehydrogenase activity increased in the muscle and decreased in the heart of the epileptic rats compared to control. Insulin and T3 content were increased significantly in the serum of the epileptic rats. Our results suggest that repetitive seizures resulted in increased metabolism and excitability in epileptic rats. Bacopa monnieri and Bacoside-A treatment prevents the occurrence of seizures there by reducing the impairment on peripheral nervous system.
Collapse
Affiliation(s)
- Jobin Mathew
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682 022, Kerala, India
| | | | | | | |
Collapse
|
|
22
|
Peeyush KT, Gireesh G, Jobin M, Paulose CS. Neuroprotective role of curcumin in the cerebellum of streptozotocin-induced diabetic rats. Life Sci 2009; 85:704-10. [PMID: 19804785 DOI: 10.1016/j.lfs.2009.09.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2009] [Revised: 09/21/2009] [Accepted: 09/23/2009] [Indexed: 10/20/2022]
Abstract
AIMS Chronic hyperglycaemia in diabetes involves a direct neuronal damage caused by intracellular glucose which leads to altered neurotransmitter functions and reduced motor activity. The present study investigated the effect of curcumin in the functional regulation of muscarinic and alpha7 nicotinic acetylcholine receptors, insulin receptors, acetylcholine esterase and Glut3 in the cerebellum of streptozotocin (STZ)-induced diabetic rats. MAIN METHODS All studies were done in the cerebellum of male Wistar rats. Radioreceptor binding assays were done for total muscarinic, M(1) and M(3) receptors using specific ligands, and the gene expression was also studied using specific probes. KEY FINDINGS Our results showed an increased gene expression of acetylcholine esterase, Glut3, muscarinic M1, M3, alpha7 nicotinic acetylcholine and insulin receptors in the cerebellum of diabetic rats in comparison to control. Scatchard analysis of total muscarinic, M1 and M3 receptors showed an increased binding parameter, B(max) in diabetic rats compared to control. Curcumin and insulin inhibited diabetes-induced elevation in the gene expression of acetylcholine esterase, Glut3, insulin and cholinergic receptors in the cerebellum of diabetic rats. SIGNIFICANCE Our studies suggest that curcumin plays a vital role in regulating the activity of cholinergic and insulin receptors and mechanism of glucose transportation through Glut3, which results in normalizing the diabetes-mediated cerebellar disorders. Thus, curcumin has a significant role in a therapeutic application for the prevention or progression of diabetic complications in the cerebellum.
Collapse
Affiliation(s)
- Kumar T Peeyush
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin - 682 022, Kerala, India
| | | | | | | |
Collapse
|
|
23
|
Spasov AA, Iezhitsa IN, Kravchenko MS, Kharitonova MV. Features of central neurotransmission in animals in conditions of dietary magnesium deficiency and after its correction. ACTA ACUST UNITED AC 2009; 39:645-53. [PMID: 19621270 DOI: 10.1007/s11055-009-9182-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2007] [Revised: 04/24/2008] [Indexed: 10/20/2022]
Abstract
Magnesium is important in the regulation of neurotransmitter metabolism and the modulation of receptor function in the CNS, including neurotransmitters and receptors involved in the pathogenesis of many mental disorders. The aim of the present work was to perform a pharmacological evaluation of the central mechanisms of action of magnesium salts in the clofelin, phenamine, arecoline, nicotine, apomorphine, and 5-hydroxytryptophan tests in conditions of dietary magnesium deficiency. After reaching the magnesium deficiency state, animals were given oral (via tube) magnesium L-asparaginate and magnesium chloride lone and in combination with vitamin B(6), as well as the reference agent Magne B6. Our assessments of phenamine stereotypy in magnesium-deficient animals showed reductions in the latent period by an average of 14.89% and a significant increase in the duration of phenamine stereotypy by an average of 19.44% (from 268.23 +/- 8.17 to 320.36 +/- 19.90 min) as compared with intact rats. Studies of hyperkinesia induced by 5-hydroxytryptophan showed a two-fold reduction in its extent in the magnesium-deficient group (p </= 0.05). Administration of arecoline to magnesium-deficient animals resulted in a statistically significant increase in the latent period from a mean of 92.75 +/- 19.35 to 245.17 +/- 121.86 sec, with a reduction in the duration of tremor from an average of 1175.58 +/- 127.87 to 703.83 +/- 89.33 sec (p </= 0.05) as compared with intact rats. In terms of its influence on the hypothermic effects of clofelin and apomorphine and the convulsive effect of nicotine, there were no significant differences between the intact group and the magnesium-deficiency animals. Administration of magnesium salts compensated for the magnesium deficiency in plasma and erythrocytes, which was accompanied by recovery of measures in the phenamine, arecoline, and 5-HT tests to levels typical of intact controls. There was a tendency for magnesium L-asparaginate and magnesium chloride combined with pyridoxine to have greater activity, and the efficacies of these treatments was no less than that of reference agent Magne B6. Thus, dietary magnesium deficiency led to impairment of neurotransmission in central serotoninergic, M-cholinergic, and noradrenergic structures and administration of magnesium salts reversed these changes.
Collapse
Affiliation(s)
- A A Spasov
- Research Institute of Pharmacology and Department of Pharmacology, Volgograd State Medical University, 1 Pavshikh Bortsov Square, 400131, Volgograd, Russia.
| | | | | | | |
Collapse
|
|
24
|
Acetylcholine and muscarinic receptor function in cerebral cortex of diabetic young and old male Wistar rats and the role of muscarinic receptors in calcium release from pancreatic islets. Biogerontology 2009; 11:151-66. [DOI: 10.1007/s10522-009-9237-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2009] [Accepted: 06/02/2009] [Indexed: 10/20/2022]
|
|
25
|
Balakrishnan S, Mathew J, Antony S, Paulose CS. Muscarinic M(1), M(3) receptors function in the brainstem of streptozotocin induced diabetic rats: their role in insulin secretion from the pancreatic islets as a function of age. Eur J Pharmacol 2009; 608:14-22. [PMID: 19347982 DOI: 10.1016/j.ejphar.2009.01.047] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
In the present study, we have investigated acetylcholine esterase (AChE) activity and muscarinic M(1), M(3) receptors kinetics in the brainstem of both young and old streptozotocin induced and insulin treated diabetic rats (D + I). Also, the functional role of acetylcholine and muscarinic receptors in insulin secretion from the pancreatic islets was studied in vitro. 90 week old control rats showed decreased V(max) (P < 0.001) for AChE compared to 7 week old control rats. V(max) was decreased (P < 0.001) in 7 week diabetic groups whereas 90 week old diabetic groups showed increased (P < 0.001) V(max) when compared to their respective controls. Binding studies using [(3)H]QNB and [(3)H]DAMP of 90 week old control showed significant increase in the B(max) (P < 0.001) and K(d) (P < 0.01) of muscarinic M(1) receptors whereas M(3) receptor number was decreased significantly (P < 0.001) with no change in affinity when compared to 7 week old control respectively. M(1) receptor number was decreased significantly (P < 0.001) whereas M(3) receptor number was increased significantly (P < 0.001) in both 7 week and 90 week old diabetic rat groups compared to their respective controls. The competition curve for [(3)H]QNB fitted for two sited model in 7 week old groups whereas fitted for one sited model in 90 week old groups. [(3)H]DAMP was fitted for two sited model in both 7 week and 90 week old groups. Insulin treatment significantly reversed (P < 0.001) the binding parameters to near control level. In vitro studies showed that acetylcholine through muscarinic M(1) and M(3) receptors stimulated insulin secretion from the pancreatic islets. Thus our studies suggest that both brainstem and pancreatic muscarinic M(1), M(3) receptors differentially regulate the cholinergic activity and insulin secretion which will have clinical significance in the management of diabetes and insulin treatment as a function of age.
Collapse
Affiliation(s)
- Savitha Balakrishnan
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India
| | | | | | | |
Collapse
|
|
26
|
Krishnakumar A, Abraham PM, Paul J, Paulose CS. Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract. J Neurol Sci 2009; 284:124-8. [PMID: 19439326 DOI: 10.1016/j.jns.2009.04.032] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2008] [Revised: 03/08/2009] [Accepted: 04/20/2009] [Indexed: 12/24/2022]
Abstract
Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory action on cerebellar function through 5HT(2C) receptors. 5-HT(2C) receptors are novel targets for developing anti-convulsant drugs. In the present study, we investigated the changes in the 5-HT(2C) receptors binding and gene expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a significant down regulation of the 5-HT content (p<0.001), 5-HT(2C) gene expression (p<0.001) and 5-HT(2C) receptor binding (p<0.001) with an increased affinity (p<0.001). Carbamazepine and B. monnieri treatments to epileptic rats reversed the down regulated 5-HT content (p<0.01), 5-HT(2C) receptor binding (p<0.001) and gene expression (p<0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the upregulation of 5-HT(2C) receptor in epileptic rats. This has clinical significance in the management of epilepsy.
Collapse
Affiliation(s)
- Amee Krishnakumar
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India
| | | | | | | |
Collapse
|
|
27
|
Robinson R, Krishnakumar A, Paulose CS. Enhanced dopamine D1 and D2 receptor gene expression in the hippocampus of hypoglycaemic and diabetic rats. Cell Mol Neurobiol 2009; 29:365-72. [PMID: 19132528 PMCID: PMC11506023 DOI: 10.1007/s10571-008-9328-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2008] [Accepted: 11/06/2008] [Indexed: 12/28/2022]
Abstract
Hypoglycaemic coma and brain injury are potential complications of insulin therapy. Hippocampal neurons are particularly vulnerable to hypoglycaemic stress leading to memory impairment. In the present article, we have investigated the dopamine (DA) content, homovanillic acid (HVA)/DA turnover ratio, DA D(1) and DA D(2) receptors in the hippocampus of insulin-induced hypoglycaemic (IIH) and streptozotocin induced diabetic rats where brain functions are impaired. The DA content decreased significantly in hippocampus of diabetic, diabetic +IIH and control +IIH rats compared to control. The HVA/DA turnover ratio also increased significantly in diabetic, diabetic +IIH and control +IIH rats compared to control. Scatchard analysis using [(3)H] DA in the hippocampus showed a significant increase in DA receptors of diabetic, diabetic +IIH and control +IIH rats with decreased affinity. Gene expression studies using Real-time PCR showed an increased expression of DA D(1) and DA D(2) receptors in the hippocampus of hypoglycaemic and diabetic rats. Our results indicate that the dopaminergic system is impaired in the hippocampus of hypoglycaemic and hyperglycaemic rats impairing DA related functions of hippocampus. We observed a prominent dopaminergic functional disturbance in the hypoglycaemic condition than in hyperglycaemia compared to control. This dopaminergic dysfunction in hippocampus during hypoglycaemia and hyperglycaemia is suggested to contribute to cognitive and memory deficits. This will have clinical significance in the treatment of diabetes.
Collapse
Affiliation(s)
- Remya Robinson
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022 Kerala India
| | - Amee Krishnakumar
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022 Kerala India
| | - C. S. Paulose
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022 Kerala India
| |
Collapse
|
|
28
|
Akash KG, Balarama KS, Paulose CS. Enhanced 5-HT(2A) receptor status in the hypothalamus and corpus striatum of ethanol-treated rats. Cell Mol Neurobiol 2008; 28:1017-25. [PMID: 18425575 PMCID: PMC11515037 DOI: 10.1007/s10571-008-9281-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2007] [Accepted: 03/27/2008] [Indexed: 10/22/2022]
Abstract
AIM Brain is the major target for the actions of ethanol and it can affect the brain in a variety of ways. In the present study we have investigated the changes in 5-HT level and the 5-HT(2A) receptors in the ethanol-treated rats. METHODS Wistar adult male rats of 180-200 g body weight were given free access to 15% (v/v) (approx.7.5 g/Kg body wt./day) ethanol for 15 days. Controls were given free access to water for 15 days. Brain 5-HT and its metabolites were assayed by high performance liquid chromatography (HPLC) integrated with an electrochemical detector (ECD) fitted with C-18-CLS-ODS reverse phase column. 5-HT(2A) receptor binding assay was done with different concentrations of [3H] MDL 100907. RESULTS The hypothalamic 5-HT content significantly increased (P < 0.001) with a decreased (P < 0.001) 5-HIAA/5-HT turnover in the ethanol-treated rats when compared to control. The corpus striatum 5-HT content significantly decreased (P < 0.01) with increased (P < 0.01) 5-HIAA/5- HT turnovers in the ethanol-treated rats when compared to control. Scatchard analysis of [(3)H] MDL 100907 against ketanserin in hypothalamus showed a significant increase (P < 0.001) in B(max )with a decreased affinity (P < 0.001) in ethanol-treated rats when compared to control. The competition curve for [3H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. An increased K(i) and log (EC(50)) value were also observed in ethanol-treated rats when compared to control. Scatchard analysis of [3H] MDL 100907 against ketanserin in the corpus striatum of ethanol-treated rats showed a significant increase (P < 0.001) in B(max) and in affinity (P < 0.01) when compared to control. The change in affinity of the receptor protein in both corpus striatum and hypothalamus shows an altered receptor. The competition curve for [(3)H] MDL 100907 against ketanserin fitted one-site model in all the groups with unity as Hill slope value. There was no significant change in K(i) and log (EC (50)) value in ethanol-treated rats when compared to control. CONCLUSION The present study demonstrated the enhanced 5-HT(2A) receptor status in hypothalamus and corpus striatum. The ethanol-induced enhanced 5-HT(2A) receptors in the hypothalamus and corpus striatum has clinical significance in the better management of ethanol addiction. This will have therapeutic application.
Collapse
Affiliation(s)
- K. G. Akash
- Molecular neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022 Kerala India
| | - K. S. Balarama
- Molecular neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022 Kerala India
| | - C. S. Paulose
- Molecular neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022 Kerala India
| |
Collapse
|
|
29
|
Adrenergic, dopaminergic and serotonergic gene expression in low dose, long time insulin and somatotropin treatment to ageing rats: rejuvenation of brain function. Biogerontology 2008; 9:429-39. [DOI: 10.1007/s10522-008-9183-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2008] [Accepted: 09/26/2008] [Indexed: 01/03/2023]
|
|
30
|
Enhanced dopamine D2 receptor function in hypothalamus and corpus striatum: their role in liver, plasma and in vitro hepatocyte ALDH regulation in ethahol treated rats. J Biomed Sci 2008; 15:623-31. [DOI: 10.1007/s11373-008-9259-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2008] [Accepted: 05/18/2008] [Indexed: 10/22/2022] Open
|
|
31
|
Gireesh G, Reas SK, Jobin M, Paulose CS. Decreased muscarinic M1 receptor gene expression in the cerebral cortex of streptozotocin-induced diabetic rats and Aegle marmelose leaf extract's therapeutic function. JOURNAL OF ETHNOPHARMACOLOGY 2008; 116:296-304. [PMID: 18201849 DOI: 10.1016/j.jep.2007.11.036] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2007] [Revised: 10/24/2007] [Accepted: 11/20/2007] [Indexed: 05/25/2023]
Abstract
AIM In the present study we have investigated the changes in the total muscarinic and muscarinic M1 receptor ([(3)H]QNB) binding and gene expression in the cerebral cortex of streptozotocin (STZ) induced diabetic, insulin and aqueous extract of Aegle marmelose leaf treated diabetic rats. MATERIALS AND METHODS Diabetes was induced in rats by intrafemoral injection of streptozotocin. Aegle marmelose leaves was given orally to one group of rats at a dosage of 1g/kg body weight per day for fourteen days. Blood glucose and plasma insulin level were measured. Muscarinic and Muscarinic M1 receptor binding studies were done in the cerebral cortex of experimental rats. Muscarinic M1 receptor gene expression was studied using real-time PCR. RESULTS Scatchard analysis for total muscarinic receptors in cerebral cortex showed that the B(max) was decreased significantly (p<0.001) in diabetic rats with a significant decrease (p<0.01) in the K(d) when compared to control group. Binding analysis of Muscarinic M1 receptors showed that B(max) was decreased significantly (p<0.001) in diabetic group when compared to control group. The K(d) also decreased significantly (p<0.01) when compared to control group. The binding parameters were reversed to near control by the treatment of diabetic rats with Aegle marmelose. Real-Time PCR analysis also showed a similar change in the mRNA levels of muscarinic M1 receptors. CONCLUSION The results showed that there is decrease in total muscarinic and muscarinic M1 receptors during diabetes which is up regulated by insulin and Aegle marmelose leaf extract treatment. This has clinical significance in therapeutic management of diabetes.
Collapse
Affiliation(s)
- Gangadharan Gireesh
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin 682 022, Kerala, India
| | | | | | | |
Collapse
|
|
32
|
Gireesh G, Kaimal SB, Kumar TP, Paulose C. Decreased muscarinic M1 receptor gene expression in the hypothalamus, brainstem, and pancreatic islets of streptozotocin-induced diabetic rats. J Neurosci Res 2008; 86:947-53. [DOI: 10.1002/jnr.21544] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
|
|
33
|
Sulaiman P, Joseph B, Kaimal SB, Paulose CS. Decreased Hepatic 5-HT1A Receptors During Liver Regeneration and Neoplasia in Rats. Neurochem Res 2007; 33:444-9. [PMID: 17721726 DOI: 10.1007/s11064-007-9452-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2007] [Accepted: 07/20/2007] [Indexed: 11/25/2022]
Abstract
In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5-HT1A receptor during liver regeneration after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in male Wistar rats. 5-HT content was significantly increased during liver regeneration after PH and NDEA induced hepatocellular carcinoma. Scatchard analysis using 8-OH-DPAT, a 5-HT1A specific agonist showed a decreased receptor during liver regeneration after PH and NDEA induced hepatocellular carcinoma. 5-HT when added alone to primary hepatocyte culture did not increase DNA synthesis but was able to increase the EGF mediated DNA synthesis and inhibit the TGF beta 1 mediated DNA synthesis suppression in vitro. This confirmed the co-mitogenic activity of 5-HT. 8-OH-DPAT at a concentration of 10(-4) M inhibited the basal and EGF-mediated DNA synthesis in primary hepatocyte cultures. It also suppressed the TGF beta 1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5-HT1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation.
Collapse
Affiliation(s)
- Pyroja Sulaiman
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala 682 022, India
| | | | | | | |
Collapse
|
|
34
|
George AK, Balarama Kaimal S, Paulose CS. Decreased dopamine D(2) receptor function in cerebral cortex and brain stem: their role in hepatic ALDH regulation in ethanol treated rats. Mol Cell Biochem 2007; 304:181-8. [PMID: 17530188 DOI: 10.1007/s11010-007-9498-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2006] [Accepted: 04/27/2007] [Indexed: 10/23/2022]
Abstract
Ethanol exerts numerous pharmacological effects through its interaction with various neurotransmitters. The dopaminergic pathway is associated with cognitive, endocrine, and motor functions, and reinforcement of addictive substances or behaviours. Aldehyde dehydrogenase (ALDH) is a vital enzyme involved with alcohol metabolism and detoxification. In the present study, we investigated the role of cerebral cortex and brain stem dopamine D(2) receptors in the functional regulation on ALDH enzyme activity, in ethanol administrated rats. Two groups of rats were selected viz. control and alcoholic. Cerebral cortex, brain stem and the liver dopamine content was decreased significantly (P < 0.05, 0.05, 0.001, respectively) and homovanillic acid/dopamine (HVA/DA) ratio has significantly increased (P < 0.05, 0.001 and 0.001), respectively in ethanol treated rats when compared to control. Scatchard analysis of [(3)H]YM-09151-2 binding to synaptic membrane preparations of cerebral cortex and brain stem showed a significant decrease (P < 0.001, 0.05, respectively) in B (max) in ethanol treated rats compared to control and the K (d) also decreased significantly (P < 0.05). The ALDH analysis showed a significant increase (P < 0.05) in V (max) in cerebral cortex, plasma and liver of experimental rats when compared with control without having significant change in brain stem but with decreased K (m) (P < 0.001). Our results suggest that decreased function of dopamine mediated through DA D(2) receptor in the cerebral cortex and brain stem enhanced the brain, plasma and liver ALDH activity in ethanol treated rats. This ALDH regulation has significance to correct alcoholics from addiction due to allergic reaction observed in aldehyde accumulation.
Collapse
Affiliation(s)
- Akash K George
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022 Kerala, India
| | | | | |
Collapse
|
|
35
|
Abstract
Vitamin B6is a water-soluble vitamin, and is readily metabolized and excreted, so it has generally been assumed to have negligible toxicity, although at very high levels of intake it can cause peripheral nerve damage. Nutritional deficiency disease is extremely rare, although a significant proportion of the population shows biochemical evidence of inadequate status, despite apparently adequate levels of intake. The vitamin has been used to treat a wide variety of conditions, which may or may not be related to inadequate intake. In some conditions use of vitamin B6supplements has been purely empirical; in other conditions there is a reasonable physiological or metabolic mechanism to explain why supplements of the vitamin many times greater than average requirements may have therapeutic uses. However, even in such conditions there is little evidence of efficacy from properly conducted controlled trials.
Collapse
|
|
36
|
Pyroja S, Joseph B, Paulose CS. Increased 5-HT2C receptor binding in the brain stem and cerebral cortex during liver regeneration and hepatic neoplasia in rats. J Neurol Sci 2007; 254:3-8. [PMID: 17258772 DOI: 10.1016/j.jns.2006.12.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2006] [Revised: 11/07/2006] [Accepted: 12/05/2006] [Indexed: 10/23/2022]
Abstract
In the present study, serotonin 2C (5-HT(2C)) receptor binding parameters in the brainstem and cerebral cortex were investigated during liver generation after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatic neoplasia in male Wistar rats. The serotonin content increased significantly (p<0.01) in the cerebral cortex after PH and in NDEA induced hepatic neoplasia. Brain stem serotonin content increased significantly (p<0.05) after PH and (p<0.001) in NDEA induced hepatic neoplasia. The number and affinity of the 5-HT(2C) receptors in the crude synaptic membrane preparations of the brain stem showed a significant (p<0.001) increase after PH and in NDEA induced hepatic neoplasia. The number and affinity of 5-HT(2C) receptors increased significantly (p<0.001) in NDEA induced hepatic neoplasia in the crude synaptic membrane preparations of the cerebral cortex. There was a significant (p<0.01) increase in plasma norepinephrine in PH and (p<0.001) in NDEA induced hepatic neoplasia, indicating sympathetic stimulation. Thus, our results suggest that during active hepatocyte proliferation 5-HT(2C) receptor in the brain stem and cerebral cortex are up-regulated which in turn induce hepatocyte proliferation mediated through sympathetic stimulation.
Collapse
Affiliation(s)
- Sulaiman Pyroja
- Molecular Neurobiology and Cell biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India
| | | | | |
Collapse
|
|
37
|
Shankar PNE, Joseph A, Paulose CS. Decreased [3H] YM-09151-2 binding to dopamine D2 receptors in the hypothalamus, brainstem and pancreatic islets of streptozotocin-induced diabetic rats. Eur J Pharmacol 2006; 557:99-105. [PMID: 17174299 DOI: 10.1016/j.ejphar.2006.11.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2006] [Revised: 11/06/2006] [Accepted: 11/09/2006] [Indexed: 11/22/2022]
Abstract
In the present study dopamine was measured in the hypothalamus, brainstem, pancreatic islets and plasma, using HPLC. Dopamine D2 receptor changes in the hypothalamus, brainstem and pancreatic islets were studied using [3H] YM-09151-2 in streptozotocin-induced diabetic and insulin-treated diabetic rats. There was a significant decrease in dopamine content in the hypothalamus (P<0.001), brainstem (P<0.001), pancreatic islets (P<0.001) and plasma (P<0.001) in diabetic rats when compared to control. Scatchard analysis of [3H] YM-09151-2 in the hypothalamus of diabetic rats showed a significant decrease in Bmax (P<0.001) and Kd, showing an increased affinity of D2 receptors when compared to control. Insulin treatment did not completely reverse the changes that occurred during diabetes. There was a significant decrease in Bmax (P<0.01) with decreased affinity in the brainstem of diabetic rats. The islet membrane preparation of diabetic rats showed a significant decrease (P<0.001) in the binding of [3H] YM-09151-2 with decreased Kd (P<0.001) compared to control. The increase in affinity of D2 receptors in hypothalamus and pancreatic islets and the decreased affinity in brainstem were confirmed by competition analysis. Thus our results suggest that the decreased dopamine D2 receptor function in the hypothalamus, brainstem and pancreas affects insulin secretion in diabetic rats, which has immense clinical relevance to the management of diabetes.
Collapse
Affiliation(s)
- P N Eswar Shankar
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India
| | | | | |
Collapse
|
|
38
|
Ani Das V, Savitha B, Paulose CS. Decreased alpha1-adrenergic receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats. Neurochem Res 2006; 31:727-34. [PMID: 16791475 DOI: 10.1007/s11064-006-9073-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2006] [Indexed: 10/24/2022]
Abstract
The purpose of this study was to investigate the role of brain alpha1-adrenergic receptor binding in the rat model of pancreatic regeneration using 60-70% pancreatectomy. The alpha1-adrenergic receptors kinetics was studied in the cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H]prazosin in cerebral cortex and brain stem showed a significant decrease (P < 0.01), (P < 0.05) in maximal binding (Bmax) with a significant decrease (P < 0.001), (P < 0.01) in the Kd in 72 h pancreatectomised rats compared with sham respectively. Competition analysis in cerebral cortex and brain stem showed a shift in affinity during pancreatic regeneration. The sympathetic activity was decreased as indicated by the significantly decreased norepinephrine level in the plasma (P < 0.001), cerebral cortex (P < 0.01) and brain stem (P < 0.001) of 72 h pancreatectomised rats compared to sham. Thus, from our results it is suggested that the central alpha1-adrenergic receptors have a functional role in the pancreatic regeneration mediated through the sympathetic pathway.
Collapse
Affiliation(s)
- V Ani Das
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682 022 Kerala, India
| | | | | |
Collapse
|
|
39
|
Das VA, Chathu F, Paulose CS. Decreased alpha2-adrenergic receptor in the brain stem and pancreatic islets during pancreatic regeneration in weanling rats. Life Sci 2006; 79:1507-13. [PMID: 16737719 DOI: 10.1016/j.lfs.2006.04.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2006] [Revised: 04/17/2006] [Accepted: 04/20/2006] [Indexed: 10/24/2022]
Abstract
Sympathetic stimulation inhibits insulin secretion. alpha(2)-Adrenergic receptor is known to have a regulatory role in the sympathetic function. We investigated the changes in the alpha(2)-adrenergic receptors in the brain stem and pancreatic islets using [(3)H]Yohimbine during pancreatic regeneration in weanling rats. Brain stem and pancreatic islets of experimental rats showed a significant decrease (p<0.001) in norepinephrine (NE) content at 72 h after partial pancreatectomy. The epinephrine (EPI) content showed a significant decrease (p<0.001) in pancreatic islets while it was not detected in brain stem at 72 h after partial pancreatectomy. Scatchard analysis of [(3)H]Yohimbine showed a significant decrease (p<0.05) in B(max) and K(d) at 72 h after partial pancreatectomy in the brain stem. In the pancreatic islets, Scatchard analysis of [(3)H]Yohimbine showed a significant decrease (p<0.001) in B(max) and K(d) (p<0.05) at 72 h after partial pancreatectomy. The binding parameters reversed to near sham by 7 days after pancreatectomy both in brain stem and pancreatic islets. This shows that pancreatic insulin secretion is influenced by central nervous system inputs from the brain stem. In vitro studies with yohimbine showed that the alpha(2)-adrenergic receptors are inhibitory to islet DNA synthesis and insulin secretion. Thus our results suggest that decreased alpha(2)-adrenergic receptors during pancreatic regeneration functionally regulate insulin secretion and pancreatic beta-cell proliferation in weanling rats.
Collapse
Affiliation(s)
- V Ani Das
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India
| | | | | |
Collapse
|
|
40
|
Renuka TR, Robinson R, Paulose CS. Increased insulin secretion by muscarinic M1 and M3 receptor function from rat pancreatic islets in vitro. Neurochem Res 2006; 31:313-20. [PMID: 16733808 DOI: 10.1007/s11064-005-9022-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2005] [Indexed: 10/24/2022]
Abstract
Parasympathetic system plays an important role in insulin secretion from the pancreas. Cholinergic effect on pancreatic beta cells exerts primarily through muscarinic receptors. In the present study we investigated the specific role of muscarinic M1 and M3 receptors in glucose induced insulin secretion from rat pancreatic islets in vitro. The involvement of muscarinic receptors was studied using the antagonist atropine. The role of muscarinic M1 and M3 receptor subtypes was studied using subtype specific antagonists. Acetylcholine agonist, carbachol, stimulated glucose induced insulin secretion at low concentrations (10(-8)-10(-5) M) with a maximum stimulation at 10(-7) M concentration. Carbachol-stimulated insulin secretion was inhibited by atropine confirming the role of muscarinic receptors in cholinergic induced insulin secretion. Both M1 and M3 receptor antagonists blocked insulin secretion induced by carbachol. The results show that M3 receptors are functionally more prominent at 20 mM glucose concentration when compared to M1 receptors. Our studies suggest that muscarinic M1 and M3 receptors function differentially regulate glucose induced insulin secretion, which has clinical significance in glucose homeostasis.
Collapse
Affiliation(s)
- T R Renuka
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Cochin , Kerala, India
| | | | | |
Collapse
|
|
41
|
Das VA, Robinson R, Paulose CS. Enhanced β-adrenergic receptors in the brain and pancreas during pancreatic regeneration in weanling rats. Mol Cell Biochem 2006; 289:11-9. [PMID: 16583134 DOI: 10.1007/s11010-006-9142-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2005] [Accepted: 01/23/2006] [Indexed: 10/24/2022]
Abstract
Adrenergic stimulation has an important role in the pancreatic beta-cell proliferation and insulin secretion. In the present study, we have investigated how sympathetic system regulates the pancreatic regeneration by analyzing Epinephrine (EPI), Norepinephrine (NE) and beta-adrenergic receptor changes in the brain as well as in the pancreas. EPI and NE showed a significant decrease in the brain regions, pancreas and plasma at 72 hrs after partial pancreatectomy. We observed an increase in the circulating insulin levels at 72 hrs. Scatchard analysis using [(3)H] propranolol showed a significant increase in the number of both the low affinity and high affinity beta-adrenergic receptors in cerebral cortex and hypothalamus of partially pancreatectomised rats during peak DNA synthesis. The affinity of the receptors decreased significantly in the low and high affinity receptors of cerebral cortex and the high affinity hypothalamic receptors. In the brain stem, low affinity receptors were increased significantly during regeneration whereas there was no change in the high affinity receptors. The pancreatic beta-adrenergic receptors were also up regulated at 72 hrs after partial pancreatectomy. In vitro studies showed that beta-adrenergic receptors are positive regulators of islet cell proliferation and insulin secretion. Thus our results suggest that the beta-adrenergic receptors are functionally enhanced during pancreatic regeneration, which in turn increases pancreatic beta-cell proliferation and insulin secretion in weanling rats.
Collapse
Affiliation(s)
- V Ani Das
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022 Kerala, India
| | | | | |
Collapse
|
|
42
|
Mohanan VV, Khan R, Paulose CS. Hypothalamic 5-HT functional regulation through 5-HT1A and 5-HT2C receptors during pancreatic regeneration. Life Sci 2005; 78:1603-9. [PMID: 16253282 DOI: 10.1016/j.lfs.2005.07.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2005] [Accepted: 07/26/2005] [Indexed: 01/21/2023]
Abstract
5-HT receptors are predominantly located in the brain and are involved in pancreatic function and cell proliferation through sympathetic nervous system. The objective of this study was to investigate the role of hypothalamic 5-HT, 5-HT1A and 5-HT2C receptor binding and gene expression in rat model of pancreatic regeneration using 60% pancreatectomy. The pancreatic regeneration was evaluated by 5-HT content, 5-HT1A and 5-HT2C receptor gene expression in the hypothalamus of sham operated, 72 h and 7 days pancreatectomised rats. 5-HT content was quantified by HPLC. 5-HT1A receptor assay was done by using specific agonist [3H]8-OH DPAT. 5-HT2C receptor assay was done by using specific antagonist [3H]mesulergine. The expression of 5-HT1A and 5-HT2C receptor gene was analyzed by RT-PCR. 5-HT content was higher in the hypothalamus of 72 h pancreatectomised rats. 5-HT1A and 5-HT2C receptors were down-regulated in the hypothalamus. RT-PCR analysis revealed decreased 5-HT1A and 5-HT2C receptor mRNA expression. The 5-HT1A and 5-HT2C receptors gene expression in the 7 days pancreatectomised rats reversed to near sham level. This study is the first to identify 5-HT1A and 5-HT2C receptor gene expression in the hypothalamus during pancreatic regeneration in rats. Our results suggest the hypothalamic serotonergic receptor functional regulation during pancreatic regeneration.
Collapse
Affiliation(s)
- Valiya Veettil Mohanan
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India
| | | | | |
Collapse
|
|
43
|
Mohanan VV, Kaimal SB, Paulose CS. Decreased 5-HT1A receptor gene expression and 5-HT1A receptor protein in the cerebral cortex and brain stem during pancreatic regeneration in rats. Neurochem Res 2005; 30:25-32. [PMID: 15756929 DOI: 10.1007/s11064-004-9682-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The present study was to investigate the role of central 5-HT and 5-HT(1A) receptor binding and gene expression in a rat model of pancreatic regeneration using 60% pancreatectomy. The pancreatic regeneration was evaluated by 5-HT content and 5-HT(1A) receptor gene expression in the cerebral cortex (CC) and brain stem (BS) of sham operated, 72 h and 7 days pancreatectomised rats. 5-HT content significantly increased in the CC (P < 0.01) and BS (P < 0.05) of 72 h pancreatectomised rats. Sympathetic activity was decreased as indicated by the significantly decreased norepinephrine (NE) and epinephrine (EPI) level (P < 0.001 and P < 0.05) in the plasma of 72 h pancreatectomised rats. 5-HT(1A) receptor density and affinity was decreased in the CC (P < 0.01) and BS (P < 0.01). These changes correlated with a diminished 5-HT(1A) receptor mRNA expression in the brain regions studied. Our results suggest that the brain 5-HT through 5-HT(1A) receptor has a functional role in the pancreatic regeneration through the sympathetic regulation.
Collapse
Affiliation(s)
- Valiya veettil Mohanan
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India
| | | | | |
Collapse
|
|
44
|
Mohanan VV, Chathu F, Paulose CS. Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats. Mol Cell Biochem 2005; 272:165-70. [PMID: 16010984 DOI: 10.1007/s11010-005-7030-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The purpose of this study was to investigate the role of central 5-HT2C receptor binding in rat model of pancreatic regeneration using 60-70% pancreatectomy. The 5-HT and 5-HT2C receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H] mesulergine in cerebral cortex showed a significant decrease (p < 0.05) in maximal binding (Bmax) without any change in Kd in 72 h pancreatectomised rats compared with sham. The decreased Bmax reversed to sham level by 7 days after pancreatectomy. In brain stem, Scatchard analysis showed a significant decrease (p < 0.01) in Bmax with a significant increase (p < 0.01) in Kd. Competition analysis in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after pancreatectomy. Thus the results suggest that 5-HT through the 5-HT2C receptor in the brain has a functional regulatory role in the pancreatic regeneration.
Collapse
Affiliation(s)
- Valiya Veettil Mohanan
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, India
| | | | | |
Collapse
|
|
45
|
Packer CS. Biochemical markers and physiological parameters as indices for identifying patients at risk of developing pre-eclampsia. J Hypertens 2005; 23:45-6. [PMID: 15643123 DOI: 10.1097/00004872-200501000-00011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
46
|
Tang FI, Wei IL. Vitamin B-6 deficiency prolongs the time course of evoked dopamine release from rat striatum. J Nutr 2004; 134:3350-4. [PMID: 15570036 DOI: 10.1093/jn/134.12.3350] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Vitamin B-6-deficient animals exhibit motor abnormalities. To investigate the possible physiologic alterations in the dopaminergic nervous system in vitamin B-6 deficiency, dopamine release in the striatum of vitamin B-6-deficient rats was determined using in vivo electrochemistry. Male Sprague-Dawley rats, 3 wk old, weighing 50-60 g, were randomly assigned to a control (7 mg pyridoxine HCl/kg diet), vitamin B-6-deficient (0 mg pyridoxine HCl/kg diet), or pair-fed (7 mg pyridoxine HCl/kg diet) group. After 8 wk of dietary treatment, plasma concentrations of pyridoxal 5'-phosphate as well as the striatal pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate were significantly lower in the vitamin B-6-deficient group than in the control and pair-fed groups. The dopamine concentrations of the striatum and the magnitude of the dopamine release after local application of KCl did not differ among the groups. However, the time required for KCl-evoked dopamine release to reach its peak level was significantly longer for the vitamin B-6-deficient rats than for controls. In addition, the decay time from the peak to one-half of the KCl-evoked dopamine release was also significantly prolonged in vitamin B-6-deficient rats compared with the control group. The results indicate that the cellular content of dopamine does not reflect the functional state of dopaminergic neurons in vitamin B-6 deficiency. The time course for release of dopamine and decay of the released dopamine is prolonged by vitamin B-6 deficiency, which might contribute to the motor abnormalities of the deficient rats.
Collapse
Affiliation(s)
- Fu-In Tang
- School of Nursing, National Yang-Ming University, Taipei 112, Taiwan
| | | |
Collapse
|
|
47
|
McCarty MF. Elevated sympathetic activity may promote insulin resistance syndrome by activating alpha-1 adrenergic receptors on adipocytes. Med Hypotheses 2004; 62:830-8. [PMID: 15082116 DOI: 10.1016/j.mehy.2003.11.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2003] [Accepted: 11/11/2003] [Indexed: 11/19/2022]
Abstract
An excess of free intracellular calcium can reduce the efficiency of insulin-mediated glucose transport by blocking the dephosphorylation of GLUT-4. Classical isoforms of protein kinase C (PKC) can interfere with insulin signalling via serine phosphorylation of IRS-1 and the insulin receptor. Parathyroid hormone (PTH), by activating phospholipase C-beta in adipocytes, can promote a sustained increase in intracellular free calcium in these cells, while also activating classical PKCs. This may rationalize the fact that insulin resistance is a typical feature of hyperparathyroidism, as well as epidemiological evidence that regular ingestion of dairy products or of ethanol--which down-regulates PTH secretion--reduces risk for insulin resistance syndrome and diabetes. Alpha-1 adrenergic receptors of adipocytes--like PTH receptors--also activate phospholipase C-beta, and thus have an effect analogous to PTH on intracellular free calcium and PKC activity in adipocytes. This suggests that, via activation of alpha-1 adrenergic receptors, increased sympathetic activity in adipose tissue may promote insulin resistance syndrome. In fact, measures which provoke increased sympathetic output--such as diuretic use and severe salt restriction--are known to compromise insulin sensitivity, whereas alpha-1 antagonist drugs, as well as drugs that act centrally to suppress sympathetic activity, typically have a favorable effect on insulin function. When insulin resistance syndrome is associated with elevated sympathetic activity--for example, in hypertensives who are obese or on diuretic therapy--measures which down-regulate sympathetic activity, or, more specifically, alpha-1 adrenergic activity, may be warranted. These include centrally acting imidazoline analogs (moxonidine, rilmenidine) and alpha-1 antagonists (doxazosin, prazosin). Taurine and high-dose pyridoxine may represent practical nutritional strategies for moderating elevated sympathetic activity, and exercise training and low-insulin-response diets may be useful in this regard as well.
Collapse
Affiliation(s)
- Mark F McCarty
- Pantox Laboratories, 4622 Santa Fe St., San Diego, CA 29109, USA.
| |
Collapse
|
|
48
|
Renuka TR, Ani DV, Paulose CS. Alterations in the muscarinic M1 and M3 receptor gene expression in the brain stem during pancreatic regeneration and insulin secretion in weanling rats. Life Sci 2004; 75:2269-80. [PMID: 15350825 DOI: 10.1016/j.lfs.2004.03.034] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2003] [Accepted: 03/02/2004] [Indexed: 11/21/2022]
Abstract
Muscarinic M1 and M3 receptor changes in the brain stem during pancreatic regeneration were investigated. Brain stem acetylcholine esterase activity decreased at the time of regeneration. Sympathetic activity also decreased as indicated by the norepinephrine (NE) and epinephrine (EPI) content of adrenals and also in the plasma. Muscarinic M1 and M3 receptors showed reciprocal changes in the brain stem during regeneration. Muscarinic M1 receptor number decreased at time of regeneration without any change in the affinity. High affinity M3 receptors showed an increase in the number. The affinity did not show any change. The number of low affinity receptors decreased with decreased Kd at 72 hours after partial pancreatectomy. The Kd reversed to control value with a reversal of the number of receptors to near control value. Gene expression studies also showed a similar change in the mRNA level of M1 and M3 receptors. These alterations in the muscarinic receptors regulate sympathetic activity and maintain glucose level during pancreatic regeneration. Central muscarinic M1 and M3 receptor subtypes functional balance is suggested to regulate sympathetic and parasympathetic activity, which in turn control the islet cell proliferation and glucose homeostasis.
Collapse
Affiliation(s)
- T R Renuka
- Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, 682 022, Kerala, India
| | | | | |
Collapse
|
|
49
|
França DS, Souza AL, Almeida KR, Dolabella SS, Martinelli C, Coelho MM. B vitamins induce an antinociceptive effect in the acetic acid and formaldehyde models of nociception in mice. Eur J Pharmacol 2001; 421:157-64. [PMID: 11516431 DOI: 10.1016/s0014-2999(01)01038-x] [Citation(s) in RCA: 89] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The effect of some B vitamins in chemical and thermal models of nociception in mice was investigated. The association thiamine/pyridoxine/cyanocobalamin (TPC, 20-200 mg/kg, i.p. or per os), thiamine, pyridoxine (50-200 mg/kg, i.p.) or riboflavin (3-100 mg/kg, i.p) induced an antinociceptive effect, not changed by naloxone (10 mg/kg, i.p.), in the acetic acid writhing model. Treatment for 7 days with thiamine/pyridoxine/cyanocobalamin (100 or 200 mg/kg, i.p.), thiamine (50 or 100 mg/kg) or pyridoxine (50 or 100 mg/kg) or acute treatment with riboflavin (6 or 12 mg/kg, i.p) inhibited the nociceptive response induced by formaldehyde. The B vitamins did not inhibit the nociceptive response in the hot-plate model. Both 7-day thiamine/pyridoxine/cyanocobalamin (100 mg/kg, i.p.) or acute riboflavin (25 or 50 mg/kg, i.p.) treatment partially reduced formaldehyde-induced hindpaw oedema. The B vitamins antinociceptive effect may involve inhibition of the synthesis and/or action of inflammatory mediators since it was not observed in the hot-plate model, was not reversed by naloxone, only the second phase of the formaldehyde-induced nociceptive response was inhibited, and formaldehyde-induced hindpaw oedema was reduced.
Collapse
Affiliation(s)
- D S França
- Laboratory of Pharmacology, Faculty of Pharmacy, Federal University of Minas Gerais, Avenida Olegário Maciel 2360, 30180-112 MG, Belo Horizonte, Brazil
| | | | | | | | | | | |
Collapse
|
|
50
|
Abstract
Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival.
Collapse
Affiliation(s)
- M F McCarty
- Pantox Laboratories, San Diego, California, USA
| |
Collapse
|