Exercise contributes to the effects of DHA dietary supplementation by acting on membrane-related synaptic systems

Department of Physiological Science, UCLA, 621 Charles E. Young Drive, Los Angeles, CA 90095, USA.
Brain research (Impact Factor: 2.84). 06/2009; 1341:32-40. DOI: 10.1016/j.brainres.2009.05.018
Source: PubMed


Dietary omega-3 fatty acid (i.e. docosohexaenoic acid (DHA)) and exercise are gaining recognition for supporting brain function under normal and challenging conditions. Here we evaluate the possibility that the interaction of DHA and exercise can involve specific elements of the synaptic plasma membrane. We found that voluntary exercise potentiated the effects of a 12-day DHA dietary supplementation regimen on increasing the levels of syntaxin 3 (STX-3) and the growth-associated protein (GAP-43) in the adult rat hippocampus region. STX-3 is a synaptic membrane-bound protein involved in the effects of DHA on membrane expansion. The DHA diet and exercise also elevated levels of the NMDA receptor subunit NR2B, which is important for synaptic function underlying learning and memory. The actions of exercise and DHA dietary supplementation reflected on enhanced learning performance in the Morris water maze as learning ability was associated with higher levels of STX-3 and NR2B. The overall findings reveal a mechanism by which exercise can interact with the function of DHA dietary enrichment to elevate the capacity of the adult brain for axonal growth, synaptic plasticity, and cognitive function.

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    • "That is, there was no evidence for an additive or multiplicative benefit of greater amounts of PA in combination with lower AA:DHA ratios on cognitive performance. Our second hypothesis, based on behavioral evidence from rodent studies (Chytrova et al., 2010), was that a high AA:DHA ratio would exacerbate the detrimental effects of physical inactivity on cognitive Fig. 1. AA:DHA ratio  kilocalories interaction with cognitive function. "
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    ABSTRACT: Greater amounts of physical activity (PA) and omega-3 fatty acids have both been independently associated with better cognitive performance. Because of the overlapping biological effects of omega-3 fatty acids and PA, fatty acid intake may modify the effects of PA on neurocognitive function. The present study tested this hypothesis by examining whether the ratio of serum omega-6 to omega-3 fatty acid levels would moderate the association between PA and executive and memory functions in 344 participants (Mean age=44.42 years, SD=6.72). The Paffenbarger Physical Activity Questionnaire (PPAQ), serum fatty acid levels, and performance on a standard neuropsychological battery were acquired on all subjects. A principal component analysis reduced the number of cognitive outcomes to three factors: n-back working memory, Trail Making test, and Logical Memory. We found a significant interaction between PA and the ratio of omega-6 to omega-3 fatty acid serum levels on Trail Making performance and n-back performance, such that higher amounts of omega-3 levels offset the deleterious effects of lower amounts of PA. These effects remained significant in a subsample (n=299) controlling for overall dietary fat consumption. There were no significant additive or multiplicative benefits of higher amounts of both omega-3 and PA on cognitive performance. Our results demonstrate that a diet high in omega-3 fatty acids might mitigate the effect of lower levels of PA on cognitive performance. This study illuminates the importance of understanding dietary and PA factors in tandem when exploring their effects on neurocognitive health.
    Neuropsychologia 07/2014; 59(1). DOI:10.1016/j.neuropsychologia.2014.04.018 · 3.30 Impact Factor
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    • "Recently, several researchers combined voluntary exercise with dietary supplementation using omega-3 docosahexaenoic (DHA) and omega-6 arachidonic (AA) fatty acids (FA). DHA supplementation potentiated the known beneficial effects of exercise on enhanced spatial learning [6]–[10], and increased expression of various molecules involved in synaptic plasticity [21], [22]. DHA and AA are polyunsaturated FA mostly acquired exogenously through diet or produced endogenously from linoleic and α-linoleic FA, which are acquired from the diet [23]–[25]. "
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    ABSTRACT: Combinatorial therapies using voluntary exercise and diet supplementation with polyunsaturated fatty acids have synergistic effects benefiting brain function and behavior. Here, we assessed the effects of voluntary exercise on anxiety-like behavior and on total FA accumulation within three brain regions: cortex, hippocampus, and cerebellum of running versus sedentary young adult male C57/BL6J mice. The running group was subjected to one month of voluntary exercise in their home cages, while the sedentary group was kept in their home cages without access to a running wheel. Elevated plus maze (EPM), several behavioral postures and two risk assessment behaviors (RABs) were then measured in both animal groups followed immediately by blood samplings for assessment of corticosterone levels. Brains were then dissected for non-targeted lipidomic analysis of selected brain regions using gas chromatography coupled to mass spectrometry (GC/MS). Results showed that mice in the running group, when examined in the EPM, displayed significantly lower anxiety-like behavior, higher exploratory and risky behaviors, compared to sedentary mice. Notably, we found no differences in blood corticosterone levels between the two groups, suggesting that the different EPM and RAB behaviors were not related to reduced physiological stress in the running mice. Lipidomics analysis revealed a region-specific cortical decrease of the saturated FA: palmitate (C16:0) and a concomitant increase of polyunsaturated FA, arachidonic acid (AA, omega 6-C20: 4) and docosahexaenoic acid (DHA, omega 3-C22: 6), in running mice compared to sedentary controls. Finally, we found that running mice, as opposed to sedentary animals, showed significantly enhanced cortical expression of phospholipase A2 (PLA2) protein, a signaling molecule required in the production of both AA and DHA. In summary, our data support the anxiolytic effects of exercise and provide insights into the molecular processes modulated by exercise that may lead to its beneficial effects on mood.
    PLoS ONE 12/2013; 8(12):e81459. DOI:10.1371/journal.pone.0081459 · 3.23 Impact Factor
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    • "As we know that TBI promotes oxidative damage of the plasma membrane [8], likely influencing the membrane’s phospholipid composition, such as DHA, we used the lipid peroxidation marker 4-HNE to assess the status of the plasma membrane in response to TBI and DHA interventions [8]. We have also assessed syntaxin-3 based on its role as a modulator of neuronal membrane expansion, especially during synaptic growth [9], and assessed calcium-independent phospholipase A-2 (iPLA-2) based on its influence on membrane phospholipid biosynthesis and turnover [10]. "
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    ABSTRACT: Although traumatic brain injury (TBI) is often associated with gait deficits, the effects of TBI on spinal cord centers are poorly understood. We seek to determine the influence of TBI on the spinal cord and the potential of dietary omega-3 (n-3) fatty acids to counteract these effects. Male rodents exposed to diets containing adequate or deficient levels of n-3 since gestation received a moderate fluid percussion injury when becoming 14 weeks old. TBI reduced levels of molecular systems important for synaptic plasticity (BDNF, TrkB, and CREB) and plasma membrane homeostasis (4-HNE, iPLA2, syntaxin-3) in the lumbar spinal cord. These effects of TBI were more dramatic in the animals exposed to the n-3 deficient diet. Results emphasize the comprehensive action of TBI across the neuroaxis, and the critical role of dietary n-3 as a means to build resistance against the effects of TBI.
    PLoS ONE 12/2012; 7(12):e52998. DOI:10.1371/journal.pone.0052998 · 3.23 Impact Factor
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