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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    • "As described in previous sections, skilled exercise may lead to the recruitment and activation of neurons in specific circuits within the brain. On the other hand, aerobic exercise may have more global effects on the entire brain including lowering the threshold for neuroplasticity to occur through the expression of neurotrophic factors or other modulators of synaptic plasticity as well as increasing rCBF [82]. However, the activation of neurons through engagement in skilled exercise and the modulation of blood flow through aerobic exercise may not be mutually exclusive processes. "
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    ABSTRACT: Animal studies have been instrumental in providing evidence for exercise-induced neuroplasticity of corticostriatal circuits that are profoundly affected in Parkinson’s disease. Exercise has been implicated in modulating dopamine and glutamate neurotransmission, altering synaptogenesis, and increasing cerebral blood flow. In addition, recent evidence supports that the type of exercise may have regional effects on brain circuitry, with skilled exercise differentially affecting frontal-striatal related circuits to a greater degree than pure aerobic exercise. Neuroplasticity in models of dopamine depletion will be reviewed with a focus on the influence of exercise on the dorsal lateral striatum and prefrontal related circuitry underlying motor and cognitive impairment in PD. Although clearly more research is needed to address major gaps in our knowledge, we hypothesize that the potential effects of exercise on inducing neuroplasticity in a circuit specific manner may occur through synergistic mechanisms that include the coupling of an increasing neuronal metabolic demand and increased blood flow. Elucidation of these mechanisms may provide important new targets for facilitating brain repair and modifying the course of disease in PD.
    10/2015; 1(1):25-35. DOI:10.3233/BPL-150021
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    • "Importantly, brain BDNF availability can be changed by non-pharmacological and non-invasive approaches, specifically by diet (Duan et al., 2001; Lee et al., 2002), exercise (Neeper et al., 1995; Cotman et al., 2007), and EE (Young et al., 1999; Wolf et al., 2006). Early EE increases conversion of pro-BDNF to BDNF in the adult rat's hippocampus (Cao et al., 2014). "
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    ABSTRACT: Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11–18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22–50. On PNDs 51–57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphineexposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF. BDNF may contribute to the beneficial effects of an enriched environment on prenatal morphine-exposed to rats.
    Neuroscience 10/2015; 305(1):372-383. DOI:10.1016/j.neuroscience · 3.36 Impact Factor
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    • "Training types may also act by additive and independent mechanisms on cognition (Wolf et al., 2006). Physical training may reduce neuroinflammation (Cotman et al., 2007), increase cerebral blood flow (Smith et al., 2010a) and velocity (Ainslie et al., 2008), decrease risk factors for cognitive decline such as cardiovascular diseases and diabetes (Cotman et al., 2007), reduce amyloid deposition (Liang et al., 2010) and increase hippocampal size (Erickson et al., 2011). Cognitive training may reduce the impairment of hippocampal long-term potentiation induced by amyloid-β oligomers (Li et al., 2013) and may reduce amyloid deposition independently from physical training (Lazarov et al., 2005; Landau et al., 2012). "
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    Frontiers in Aging Neuroscience 08/2015; 7(152). DOI:10.3389/fnagi.2015.00152 · 4.00 Impact Factor
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