title: 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.
authors.affiliation: Institute for Brain Science and Technology, Inje University, Busan, Republic of Korea.
authors.forename: Zheng Huan
authors.initials: ZH
authors.lastname: Fang
authors.forename: Chan Hong
authors.initials: CH
authors.lastname: Lee
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Seo
authors.forename: Hyeyeon
authors.initials: H
authors.lastname: Cho
authors.forename: Jung Goo
authors.initials: JG
authors.lastname: Lee
authors.forename: Bong Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological; D013569:Synapses / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
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