Exploration for the mechanism of exercise-induced neural activation and protection

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By using a line of transgenic mouse line in which GFP expression is driven by a neural activity-dependent promoter, we mapped brain areas where neural activity is upregulated after exercise. In mice underwent voluntary exercise on running wheels, GFP fluorescence became significantly more intense than the control mice in the following areas : hippocampus(medial CA1 area, pyramidal layer, medial dentate gyrus), entorhinal cortex, somatosensory area(S1). Since a subset of the dentate gyrus neurons were positive in GFP and phosphorylated TrkB(indicating activation of the major BDNF receptor) we conducted proteomic analysis of this area using comparative shotgun LC-MS/MS method. The data indicated that a few cytoskeletal proteins, adaptor proteins, metabolic enzymes(whose identities will be disclosed upon publication of the study) were significantly upregulated in activity-dependent manner. After validation with immunoblot and immunohistochemistry, we focused on one candidate protein whose cognate gene knockout mouse line had been deposited in a public repository. We have already completed backcrossing of the line to the C57BL/6N background. Using mice with or without the candidate gene, we are preparing for comparative analysis on exercise-mediated biochemical, metabolic, behavioral changes and susceptibility against oxidataive and/or proteotoxic stresses.