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

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. Copyright 2009. Published by Elsevier B.V.