Abstract
This article reviewed the beneficial effects of moderate voluntary physical exercise on brain health according to the studies on humans and animals, which includes improving psychological status and cognitive function, enhancing psychological well-being, decreasing the risks of Alzheimer’s disease (AD) and dementia, and promoting the effects of antidepressant and anxiolytic. The possible underlying neurobiological mechanisms are involved up-active and down-active pathways. The up-active pathway is associated with enhancements of several neurotransmitters systems afferent to hippocampus, including norepinephrine (NE), serotonin (5-Hydroxytryptamine, 5-HT), acetylcholine (ACh) and γ-aminobutyric acid (GABA). The down-active pathway is mainly concerned with up-regulation of the brain-derived neurotrophic factor (BDNF) and neurogenesis. It is suggested that NE activation via β-adrenergic receptors may be essential for exercise-induced BDNF up-regulation. The possible intracellular signaling pathways of NE-mediated BDNF up-expression may be involved in GPCR-MAPK-PI-3K crosstalk and positive feedback.
Keywords: exercise, brain, cognition, norepinephrine, serotonin, brain-derived neurotrophic factor
摘要
本文综述了在人和动物方面有关自愿适量运动有益于脑作用的研究, 包括改善心理状态和认知功能、 增强心理幸福感、 降低老年痴呆症发生危险度和发挥抗抑郁及抗焦虑药的作用等。 运动对脑的作用机制包含上游和下游 两方面: 上游途径主要涉及投射到海马的几种神经递质系统的功能增强, 其中包括去甲肾上腺素、5-羟色胺、 乙 酰胆碱和γ-氨基丁酸; 下游途径主要涉及脑源性神经营养因子的表达提高和神经元发生的增强; 其中, 激活 β 受 体介导的去甲肾上腺素能神经的传递被认为是运动导致脑源性神经营养因子表达增强的前提, 上述过程在细胞内的可能信号转导机制主要涉及G-蛋白偶联受体-促分裂原活化蛋白激酶-磷脂酰肌醇(−3)激酶等细胞信号转导通路的交互及正反馈调控。
关键词: 运动, 脑, 认知, 去甲肾上腺素, 5-羟色胺, 脑源性神经营养因子
References
- [1].Dishman R.K., Berthoud H.R., Booth F.W., Cotman C.W., Edgerton V.R., Fleshner M.R., et al. Neurobiology of Exercise. Obesity (Silver Spring) 2006;14:345–356. doi: 10.1038/oby.2006.46. [DOI] [PubMed] [Google Scholar]
- [2].DiLorenzo T.M., Bargman E.P., Stucky-Ropp R., Brassington G.S., Frensch P.A., LaFontaine T. Long-term effects of aerobic exercise on psychological outcomes. Prev Med. 1999;28:75–85. doi: 10.1006/pmed.1998.0385. [DOI] [PubMed] [Google Scholar]
- [3].Hassmén P., Koivula N., Uutela A. Physical exercise and psychological well-being: a population study in Finland. Prev Med. 2000;30:17–25. doi: 10.1006/pmed.1999.0597. [DOI] [PubMed] [Google Scholar]
- [4].Netz Y., Wu M.J., Becker B.J., Tenenbaum G. Physical activity and psychological well-being in advanced age: a meta-analysis of intervention studies. Psychol Aging. 2005;20:272–284. doi: 10.1037/0882-7974.20.2.272. [DOI] [PubMed] [Google Scholar]
- [5].Colcombe S., Kramer A.F. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci. 2003;14:125–130. doi: 10.1111/1467-9280.t01-1-01430. [DOI] [PubMed] [Google Scholar]
- [6].Salmon P. Effects of physical exercise on anxiety, depression and sensitivity to stress: a unifying theory. Clin Psychol Rev. 2001;21:33–61. doi: 10.1016/S0272-7358(99)00032-X. [DOI] [PubMed] [Google Scholar]
- [7].Friedland R.P., Fritsch T., Smyth K.A., Koss E., Lerner A.J., Chen C.H., et al. Patients with Alzheimer’s disease has reduced activities in midlife compared with healthy control-group members. Proc Natl Acad Sci USA. 2001;98:3440–3445. doi: 10.1073/pnas.061002998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Laurin D., Verreault R., Lindsay J., MacPherson K., Rockwood K. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol. 2001;58:498–504. doi: 10.1001/archneur.58.3.498. [DOI] [PubMed] [Google Scholar]
- [9].Paul A.A., Victoria M.P., Viorela P. Voluntary Exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J Neurosci. 2005;25:4217–4221. doi: 10.1523/JNEUROSCI.0496-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Neeper S.A., Gómez-Pinilla F., Choi J., Cotman C. Exercise and brain neurotrophins. Nature. 1995;373:109. doi: 10.1038/373109a0. [DOI] [PubMed] [Google Scholar]
- [11].Oliff H.S., Berchtold N.C., Isackson P., Cotman C.W. Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. Brain Res Mol Brain Res. 1998;61:147–53. doi: 10.1016/S0169-328X(98)00222-8. [DOI] [PubMed] [Google Scholar]
- [12].Antonio A.G., Tony G.H., Celithelma G., Chen M.J., Russo-Neustadt A.A. Exercise antidepressant treatment and BDNF mRNA expression in the aging brain. Pharmacol Biochem Behav. 2004;77:209–220. doi: 10.1016/j.pbb.2003.10.020. [DOI] [PubMed] [Google Scholar]
- [13].Cotman C.W., Berchtold N.C. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002;25:295–301. doi: 10.1016/S0166-2236(02)02143-4. [DOI] [PubMed] [Google Scholar]
- [14].Duman R.S., Monteggia L.M. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006;59:1116–1127. doi: 10.1016/j.biopsych.2006.02.013. [DOI] [PubMed] [Google Scholar]
- [15].Duman R.S. Neurotrophic factors and regulation of mood: role of exercise, diet and metabolism. Neurobiol Aging. 2005;26(Suppl1):88–93. doi: 10.1016/j.neurobiolaging.2005.08.018. [DOI] [PubMed] [Google Scholar]
- [16].Farmer J., Zhao X., Van P.H., Wodtke K., Gage F.H., Christie B.R. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-dawley rats in vivo. Neuroscience. 2004;124:71–79. doi: 10.1016/j.neuroscience.2003.09.029. [DOI] [PubMed] [Google Scholar]
- [17].van Praag H., Shubert T., Zhao C., Gage F.H. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci. 2005;25:8680–8685. doi: 10.1523/JNEUROSCI.1731-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [18].Dunn A.L., Reigle T.G., Youngstedt S.D., Armstrong R.B., Dishman R.K. Brain norepinephrine and metabolites after treadmill training and wheel running in rats. Med Sci Sports Exerc. 1996;28:204–209. doi: 10.1097/00005768-199602000-00008. [DOI] [PubMed] [Google Scholar]
- [19].Sarbadhikari S.N., Saha A.K. Moderate exercise and chronic stress produce counteractive effects on different areas of the brain by acting through various neurotransmitter receptor subtypes: a hypothesis. Theor Biol Med Model. 2006;23:33–43. doi: 10.1186/1742-4682-3-33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Garcia C., Chen M.J., Garza A.A., Cotman C.W., Russo-Neustadt A.A. The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal BDNF transcripts following voluntary physical activity. Neuroscience. 2003;119:721–732. doi: 10.1016/S0306-4522(03)00192-1. [DOI] [PubMed] [Google Scholar]
- [21].Mark P.M., Atuart M., Bronwen M. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 2004;27:589–594. doi: 10.1016/j.tins.2004.08.001. [DOI] [PubMed] [Google Scholar]
- [22].Chen M.J., Nguyen T.V., Pike C.J., Russo-Neustadt A.A. Norepinephrine induces BDNF and activates the PI-3K and MAPK cascades in embryonic hippocampal neurons. Cell Signal. 2007;19:114–128. doi: 10.1016/j.cellsig.2006.05.028. [DOI] [PubMed] [Google Scholar]
- [23].Gobbi G., Blier P. Effect of neurokinin-1 receptor antagonists on serotoninergic, noradrenergic and hippocampal neurons: Comparison with antidepressant drugs. Peptides. 2005;26:1383–1393. doi: 10.1016/j.peptides.2005.03.032. [DOI] [PubMed] [Google Scholar]
- [24].Ivy A.S., Rodriguez G., Garcia C., Chen M.J., Russo-Neustadt A.A. Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant. Pharmacol Biochem Behav. 2003;75:81–88. doi: 10.1016/S0091-3057(03)00044-3. [DOI] [PubMed] [Google Scholar]
- [25].Xu C.X., Liu H.T., Wang J. Changes of 5-hydroxytryptamine and tryptophan hydroxylase expression in the ventral horn of spinal cord. Neurosci Bull. 2008;24:29–32. doi: 10.1007/s12264-008-1031-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
