Effect of treadmill exercise on the BDNF-mediated pathway in the hippocampus of stressed rats

Abstract

A growing body of evidence suggests that exercise enhances hippocampal plasticity and function through BDNF up-regulation, which is potentiated by antidepressant treatment. However, little is known about the molecular mechanisms mediating the effect of exercise. The present study investigated the effect of treadmill exercise on PI3K/Akt signaling, which mediates synaptic plasticity in the hippocampus of stressed rats. Rats were subjected to immobilization stress 2h/day for 7 days. The rats were run on the treadmill at a speed of 15m/min, 30min/day, for 5 days. Western blotting was used to assess changes in the levels of phospho-tyr(490)-Trk receptor, phospho-ser(473)-Akt, phospho-ser(9)-GSK-3β, phospho-ser(2448)- mTOR, and phosphor-thr(389)-p70S6K, and in BDNF and various synaptic proteins. Immobilization stress significantly decreased BDNF expression and phosphorylation of Trk receptor, Akt, GSK-3β, mTOR, and p70S6K in the hippocampus of rats; furthermore, synaptophysin, PSD-95, neuroligin 1, and β-neurexin were decreased. Treadmill exercise significantly attenuated the decreased expression of these proteins. Moreover, exercise significantly increased PI3K/Akt signaling in the absence of immobilization stress. These results suggest that treadmill exercise reverses stress-induced changes in the rat hippocampus via an increase in PI3K/Akt signaling and may induce a functional reconnection of hippocampal synapses that mediate antidepressant actions.

Keywords: 5-HT; BDNF; Brain-derived neurotrophic factor; CREB; ERK; FST; G-protein coupled receptor; GPCR; GSK-3β; Glycogen synthase kinase-3β; HPA; Immobilization stress; MAPK; MTOR; N-Methyl-d-aspartate; NE; NLG 1; NMDA; PI3K; PKA; PSD-95; Phosphatidylinositol 3-kinase; SYP; Synaptic proteins; Treadmill exercise; cAMP response element binding protein; extracellular signal-regulated kinase; forced-swimming test; hypothalamus–pituitary–adrenal; mTOR; mammalian target of rapamycin; mitogen-activated protein kinase; neuroligin 1; norepinephrine; p70 ribosomal protein S6 kinase; p70S6K; postsynaptic density protein-95; protein kinase A; serotonin; synaptophysin.