Exercise Builds Brain Health: Key Roles of Growth Factor Cascades and Inflammation

University of California, Irvine Institute for Brain Aging and Dementia, 1113 Gillespie Building, Irvine, CA 92617-4540, USA.
Trends in Neurosciences (Impact Factor: 13.56). 10/2007; 30(9):464-72. DOI: 10.1016/j.tins.2007.06.011
Source: PubMed


Human and other animal studies demonstrate that exercise targets many aspects of brain function and has broad effects on overall brain health. The benefits of exercise have been best defined for learning and memory, protection from neurodegeneration and alleviation of depression, particularly in elderly populations. Exercise increases synaptic plasticity by directly affecting synaptic structure and potentiating synaptic strength, and by strengthening the underlying systems that support plasticity including neurogenesis, metabolism and vascular function. Such exercise-induced structural and functional change has been documented in various brain regions but has been best-studied in the hippocampus - the focus of this review. A key mechanism mediating these broad benefits of exercise on the brain is induction of central and peripheral growth factors and growth factor cascades, which instruct downstream structural and functional change. In addition, exercise reduces peripheral risk factors such as diabetes, hypertension and cardiovascular disease, which converge to cause brain dysfunction and neurodegeneration. A common mechanism underlying the central and peripheral effects of exercise might be related to inflammation, which can impair growth factor signaling both systemically and in the brain. Thus, through regulation of growth factors and reduction of peripheral and central risk factors, exercise ensures successful brain function.

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Available from: Nicole C Berchtold
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    • "It has been well established that exercise increases neurotrophin levels and this enhancement can persist for weeks (Berchtold et al., 2010). Although several growth factors (BDNF, VEGF, NGF) are up-regulated within the hippocampus and other regions, such as MS/DB, after exercise (Fabel et al., 2003; Griesbach et al., 2009; Neeper et al., 1996; Tong et al., 2012; Vivar et al., 2012), BDNF has emerged as the key player modulating memory improvement (Cotman et al., 2007; Gomez-Pinilla et al., 2008; Vaynman et al., 2004). Our data demonstrate that in the hippocampus both β-NGF and mBDNF are increased immediately proceeding exercise and stay elevated, albeit at descending levels, through out the 2-wk adaption period. "
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    ABSTRACT: Exercise has been shown to improve cognitive functioning in a range of species, presumably through an increase in neurotrophins throughout the brain, but in particular the hippocampus. The current study assessed the ability of exercise to restore septohippocampal cholinergic functioning in the pyrithiamine-induced thiamine deficiency (PTD) rat model of the amnestic disorder Korsakoff Syndrome. After voluntary wheel running or sedentary control conditions (stationary wheel attached to the home cage), PTD and control rats were behaviorally tested with concurrent in vivo microdialysis, at one of two time points: 24-h or 2-weeks post-exercise. It was found that only after the 2-week adaption period did exercise lead to an interrelated sequence of events in PTD rats that included: (1) restored spatial working memory; (2) rescued behaviorally-stimulated hippocampal acetylcholine efflux; and (3) within the medial septum/diagonal band, the re-emergence of the cholinergic (choline acetyltransferase [ChAT +]) phenotype, with the greatest change occurring in the ChAT +/nestin + neurons. Furthermore, in control rats, exercise followed by a 2-week adaption period improved hippocampal acetylcholine efflux and increased the number of neurons co-expressing the ChAT and nestin phenotype. These findings demonstrate a novel mechanism by which exercise can modulate the mature cholinergic/nestin neuronal phenotype leading to improved neurotransmitter function as well as enhanced learning and memory.
    Full-text · Article · Jan 2016 · Experimental Neurology
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    • "Broadly speaking, the proposed mechanisms that may involve cognitive benefits belong to two main areas: neurobiological mechanisms on one hand and psychological mechanisms on the other hand (Audiffren and André, 2015; Audiffren, André, & Albinet, 2011). An increasing amount of literature has documented the neurobiological benefits of aerobic exercise and has shown that the exercise-induced release of neurotrophic factors that facilitate neurogenesis, angiogenesis, and neurovasculature may play an important role in brain plasticity and cognition (Cotman, Berchtold, & Christie, 2007; Hillman, Erickson, & Kramer, 2008; Voelcker-Rehage and Niemann, 2013 ). These mechanisms are thought to strongly rely on the cardiovascular benefits due to chronic aerobic exercise (Albinet, Mandrick, Bernard, Perrey, & Blain, 2014). "
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    ABSTRACT: The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness, cardiac vagal control (HRV) and psychological variables. Thirty-six sedentary seniors aged 60–75 years were randomly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks. Executive functions (inhibition, updating of working memory and cognitive flexibility) and cardiorespiratory fitness (estimated VO2max) were assessed at the start, after 10 weeks of program and at the end of the program. Resting HRV and measures of psychological outcomes (depression, self-efficacy, decisional balance) were obtained at the start and at the end of the program. Participants of both groups significantly improved their VO2max level, their psychological state and their performance for the 2-back task. Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program. Only improvements in cardiac vagal control and in inhibition were shown to be functionally related. These results are discussed in line with the model of neurovisceral integration.
    Full-text · Article · Jan 2016 · Biological psychology
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    • "Exerciseinduced brain plasticity is thought to be regulated in part by the complex, pleiotropic actions of different neurotrophins, namely brainderived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). These neurotrophins are associated with synaptic plasticity, neuronal survival, and differentiation (Kang and Schuman, 1995; McAllister et al., 1999; Trejo et al., 2001; see Cotman et al., 2007 for a review ). In animal models BDNF mRNA expression, while highest in the hippocampus, is also high in EC and perirhinal cortex (Conner et al., 1997; Okuno et al., 1999). "
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    ABSTRACT: Converging evidence supports the hypothesis effects of aerobic exercise and environmental enrichment are beneficial for cognition, in particular for hippocampus-supported learning and memory. Recent work in humans suggests exercise training induces changes in hippocampal volume, but it is not known if aerobic exercise and fitness also impact the entorhinal cortex. In animal models, aerobic exercise increases expression of growth factors, including brain derived neurotrophic factor (BDNF). This exercise-enhanced expression of growth hormones may boost synaptic plasticity, and neuronal survival and differentiation, potentially supporting function and structure in brain areas including but not limited to the hippocampus. Here, using voxel based morphometry and a standard graded treadmill test to determine cardio-respiratory fitness (Bruce protocol; VO2 max), we examined if entorhinal and hippocampal volumes were associated with cardio-respiratory fitness in healthy young adults (N = 33). In addition, we examined if volumes were modulated by recognition memory performance and by serum BDNF, a putative marker of synaptic plasticity. Our results show a positive association between volume in right entorhinal cortex and cardio-respiratory fitness. In addition, average gray matter volume in the entorhinal cortex, bilaterally, was positively associated with memory performance. These data extend prior work on the cerebral effects of aerobic exercise and fitness to the entorhinal cortex in healthy young adults thus providing compelling evidence for a relationship between aerobic fitness and structure of the medial temporal lobe memory system.
    Full-text · Article · Nov 2015 · NeuroImage
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