Article

Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20: 2580-2590

Department of Physiological Science, UCLA, 621 Charles E. Young Drive, Los Angeles, CA 90095, USA.
European Journal of Neuroscience (Impact Factor: 3.18). 12/2004; 20(10):2580-90. DOI: 10.1111/j.1460-9568.2004.03720.x
Source: PubMed

ABSTRACT

We found that a short exercise period enhanced cognitive function on the Morris water maze (MWM), such that exercised animals were significantly better than sedentary controls at learning and recalling the location of the platform. The finding that exercise increased brain-derived neurotrophic factor (BDNF), a molecule important for synaptic plasticity and learning and memory, impelled us to examine whether a BDNF-mediated mechanism subserves the capacity of exercise to improve hippocampal-dependent learning. A specific immunoadhesin chimera (TrkB-IgG), that mimics the BDNF receptor, TrkB, to selectively bind BDNF molecules, was used to block BDNF in the hippocampus during a 1-week voluntary exercise period. After this, a 2-trial-per-day MWM was performed for 5 consecutive days, succeeded by a probe trial 2 days later. By inhibiting BDNF action we blocked the benefit of exercise on cognitive function, such that the learning and recall abilities of exercising animals receiving the BDNF blocker were reduced to sedentary control levels. Inhibiting BDNF action also blocked the effect of exercise on downstream systems regulated by BDNF and important for synaptic plasticity, cAMP response-element-binding protein (CREB) and synapsin I. Specific to exercise, we found an association between CREB and BDNF expression and cognitive function, such that animals who were the fastest learners and had the best recall showed the highest expression of BDNF and associated CREB mRNA levels. These findings suggest a functional role for CREB under the control of BDNF in mediating the exercise-induced enhancement in learning and memory. Our results indicate that synapsin I might also contribute to this BDNF-mediated mechanism.

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    • "Although decreased levels of these factors have been associated with agerelated hippocampal dysfunction and memory impairment, increasing BDNF by aerobic exercise seems to ameliorate hippocampal deterioration and improve memory function (for reviews, see Erickson et al., 2012; Cotman and Berchtold, 2002). In rodents, exercise has been shown to increase BDNF expression in the hippocampus and cortical regions (e.g., Neeper et al., 1995; Aguiar et al., 2008, 2011; Vaynman et al., 2004; Uysal et al., 2015), and BDNF increase has been related to exercise-induced benefits on hippocampal-dependent memory (Vaynman et al., 2004). Rodent studies have also found significant links between serum and cortical BDNF levels (Karege et al., 2002), suggesting that peripheral serum BDNF might serve as a proxy for cortical concentrations. "

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    • "Although decreased levels of these factors have been associated with agerelated hippocampal dysfunction and memory impairment, increasing BDNF by aerobic exercise seems to ameliorate hippocampal deterioration and improve memory function (for reviews, see Erickson et al., 2012; Cotman and Berchtold, 2002). In rodents, exercise has been shown to increase BDNF expression in the hippocampus and cortical regions (e.g., Neeper et al., 1995; Aguiar et al., 2008, 2011; Vaynman et al., 2004; Uysal et al., 2015), and BDNF increase has been related to exercise-induced benefits on hippocampal-dependent memory (Vaynman et al., 2004). Rodent studies have also found significant links between serum and cortical BDNF levels (Karege et al., 2002), suggesting that peripheral serum BDNF might serve as a proxy for cortical concentrations. "
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    ABSTRACT: Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77 years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.
    Full-text · Article · Nov 2015 · NeuroImage
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    • "These studies demonstrated that the benefits of exercise at the cellular level likely due to its ability to increase the production of BDNF and other signaling molecules in sleep-deprived male (Zagaar et al., 2012) and female (Saadati et al., 2014a) rats. Hippocampal BDNF can mediate the effect of exercise on cognitive functions (Vaynman et al., 2004). Therefore physical exercise could prevent the decreasing effect of SD in the OVX female rats.Of course we did not focus on the role of signaling molecule in the present study. "
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    ABSTRACT: Previous studies have been shown that exercise can improve short-term spatial learning, memory and synaptic plasticity impairments in sleep deprived female rats. The aim of the present study was to investigate the effects of treadmill exercise on sleep deprivation (SD) induced impairment in hippocampal dependent long-term memory in female rats. Intact and ovariectomized female rats were used in the current study. Exercise protocol was 4 weeks treadmill running. Twenty four hour SD was induced by using multiple platform apparatus after learning phase. Spatial learning and long-term memory was examined by using the Morris Water Maze (MWM) test. Our results indicated that sleep deprivation impaired long term memory in the intact and ovariectomized female rats, regardless of reproductive status (p<0.05) and treadmill exercise compensated this impairment (p<0.05). In conclusion the results of the current study confirmed the negative effect of SD on cognitive functions and regular exercise seems to protect rats from these factors, however more investigations need to be done. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · Behavioural processes
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