Trends in Neurosciences
OpinionExercise: a behavioral intervention to enhance brain health and plasticity
Section snippets
Exercise and neurotrophic factors
It is possible that some of the beneficial aspects of exercise act directly on the molecular machinery of the brain itself, rather than on general health (as was widely assumed in the early 1990s). To explore this hypothesis, we sought a protocol for an animal study in which exercise would be isolated as the central variable, and that would parallel aspects of human exercise studies. Voluntary wheel-running was selected because it allows rats or mice to choose how much to run (i.e. it avoids
Roles of neuronal activity and neurotransmitters
Neuronal activity and neurotransmitter interactions control BDNF gene expression patterns in the hippocampus, with glutamate-mediated signaling being the likely central convergence point. Several modulatory neurotransmitters that converge on glutamatergic neurons, including ACh, GABA and monoamines, could affect BDNF expression.
The medial septum, being a source of cholinergic and GABAergic afferents to the hippocampus, might participate in the upregulation of BDNF in response to exercise. As
Regulation by peripheral as well as central mechanisms
Although CNS activity-dependent mechanisms are pivotal in driving exercise-induced changes in levels of BDNF mRNA in the brain, it is now emerging that peripheral mechanisms are also important. Components contributing to this peripheral control include estrogen, corticosterone and insulin-like growth factor-1 (IGF-1).
Gene microarray expression patterns that support brain plasticity
In addition to BDNF, a number of other molecular systems that can mediate benefits to the brain are potentially regulated by exercise. To identify other molecular targets, the gene expression profiles of ∼5000 genes in the rat hippocampus were examined using high-density oligonucleotide arrays [55]. Three weeks of exercise led to changes – both increases and decreases – in the expression of a number of genes. Many of these genes are involved in synaptic function and plasticity, for example,
Promotion of neurogenesis
The effect of exercise on genes encoding neurotrophins and other proteins predicts that exercise could regulate downstream anatomical changes that support brain plasticity. Recently, it has been demonstrated that exercise increases the number of new neurons in the DG of adult animals [56]. Trophic factors, such as BDNF, IGF-1 and FGF-2, might mediate this effect. Exercise increases levels of BDNF in the DG (the progenitor-cell layer of the hippocampus) and BDNF promotes the survival of newly
Common mechanisms underlying plasticity induced by exercise, behavioral enrichment and learning
A robust literature documents that experience and behavior activate brain plasticity mechanisms and remodel neuronal circuitry in the brain. Exercise and behavioral enrichment paradigms, such as environmental enrichment [64], rehabilitation training 65., 66. and learning 67., 68., affect common endpoints in the brain, including regulation of growth factors, neurogenesis and structural changes. The similarities between the effects of exercise and these well-established paradigms support the
Conclusion
Exercise is a simple and widely practised behavior that activates molecular and cellular cascades that support and maintain brain plasticity. It induces expression of genes associated with plasticity, such as that encoding BDNF, and in addition promotes brain vascularization, neurogenesis, functional changes in neuronal structure and neuronal resistance to injury. Significantly, these effects occur in the hippocampus, a brain region central to learning and memory. BDNF availability could be
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