Figure 2: Schematic diagram of the functional role of skeletal muscle-derived neurotrophic factors after exercise. Exercise (neuromuscular activity) increases BDNF expression in skeletal muscle. In the patients with spinal cord injury, BDNF stimulates protein synthesis by activating Akt/mTOR/p70S6K pathway through TrkB receptor on muscle membrane. BDNF also promotes the fat oxidation through AMPK-ACC signaling. BDNF produced by skeletal muscle after exercise may circulate into brain to improve the impaired learning and/or depression. Increased GDNF protein after exercise promotes the amount of neurotransmitter (e.g., ACh) at NMJ by conjugating with Ret in presynaptic region (axon terminal). NT-4/5 may possess similar role of GDNF. BDNF: brain-derived neurotrophic factor, GDNF: glial cell-line derived neurotrophic factor, NT-4/5: neurotrophin-4/5, NMJ: neuromuscular junction, TORC1: a component of TOR signaling complex 1, Rheb: Ras homolog enriched in brain, mTOR: mammalian target of rapamycin, AMPK: AMP-activated protein kinase, and ACC: acetyl CoA carboxylase.