关键词： 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

Mesh ： Animals Brain-Derived Neurotrophic Factor / metabolism Glycogen Synthase Kinase 3 / metabolism Glycogen Synthase Kinase 3 beta Hippocampus / metabolism Male Neuronal Plasticity / physiology Neurons / metabolism Physical Conditioning, Animal / methods Proto-Oncogene Proteins c-akt / metabolism Rats Rats, Sprague-Dawley Signal Transduction / physiology Stress, Physiological Synapses / metabolism

来  源：   DOI：10.1016/j.neures.2013.04.005   PDF(Sci-hub)

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.
摘要：
越来越多的证据表明，运动通过BDNF上调增强海马可塑性和功能，这是由抗抑郁治疗增强。然而,对调节运动效果的分子机制知之甚少。本研究调查了跑步机运动对PI3K/Akt信号的影响，介导应激大鼠海马的突触可塑性。对大鼠进行固定应激2小时/天,持续7天。大鼠在跑步机上以15m/min的速度运行，30分钟/天,5天。蛋白质印迹用于评估磷酸酪氨酸（490）-Trk受体水平的变化，phospho-ser(473)-Akt,磷酸-ser(9)-GSK-3β，phospho-ser(2448)-mTOR，和荧光粉-thr(389)-p70S6K，以及BDNF和各种突触蛋白。固定化应激显著降低BDNF的表达和Trk受体的磷酸化，Akt,GSK-3β,mTOR,和p70S6K在大鼠海马中；此外，突触素,PSD-95，神经凝集素1和β-纽尿素降低。跑步机运动可显着减弱这些蛋白质的表达降低。此外，在没有固定应激的情况下,运动显著增加PI3K/Akt信号传导.这些结果表明，跑步机运动通过增加PI3K/Akt信号传导来逆转大鼠海马中应激诱导的变化，并可能诱导介导抗抑郁作用的海马突触的功能重新连接。
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