有氧运动对慢性应激大鼠脑海马区神经可塑性的影响

Effects of Aerobic Exercise on Neural Plasticity in Hippocampus of Rats with Chronic Stress

目的:以神经元和神经胶质细胞相关神经生物学变化为切入点,探讨有氧运动对慢性应激大鼠脑海马区神经可塑性的影响。方法:以SD大鼠为研究对象,按照体重均衡分为对照组(CON)、慢性应激模型组(MOD)、氟西汀组(FLU)、低强度运动组(LIR)和中等强度运动组(MIR)。给予大鼠4周慢性应激,并分别伴随氟西汀给药、低强度或者中等强度的运动干预。4周后,通过开场实验、蔗糖饮水实验、新奇抑制摄食实验以及新物体识别实验检测有氧运动对慢性应激大鼠抑郁样行为、焦虑样行为以及认知障碍的影响;同时,利用酶联免疫法和蛋白免疫印迹法,检测有氧运动对慢性应激大鼠血清皮质酮、海马内前炎因子IL1-β,以及蛋白GFAP、S100β、BDNF、p-ERK、p-CREB表达的影响,探讨有氧运动抗抑郁的行为学效应和作用机制。结果:1)低强度和中等强度运动能够显著增加慢性应激大鼠的开场活动、缩短新奇抑制摄食潜伏期,同时提高慢性应激大鼠新物体的识别指数;2)有氧运动有效逆转了慢性应激大鼠血清皮质酮的异常升高,同时降低海马内前炎性因子IL1-β的分泌;3)有氧运动可显著提升胶质细胞的标志性功能蛋白GFAP和S100β的表达水平,增强慢性应激大鼠的BDNF/ERK/CREB信号转导通路中重要蛋白BDNF、p-ERK、pCREB的表达。结论:有氧运动可以通过提高慢性应激大鼠脑海马区神经可塑性来达到抗抑郁的目的。可能与以下因素有关:1)有氧运动调节血清皮质酮的异常升高,降低海马内前炎性因子的释放,同时,提高与神经胶质细胞相关蛋白GFAP和S100β活性,从而起到神经元保护的作用;2)有氧运动可以通过激活CREB、BDNF以及ERK等重要信号蛋白的表达,提高神经营养作用,促进神经元的生长,增加神经可塑性和神经发生来发挥抗抑郁作用。

Purpose ： The purpose of this study was to investigate the effects of aerobic exercise on neural plasticity in hippocampus of rats with chronic stress by analyzing the neurobiological changes of neurons and glial cells. Methods： Fifty male Sprague-Dawley rats were randomly divided into five groups, including control group （CON） , chronic stress model group （ MOD ） , CUS ＋ fluoxetine group （ FLU ） , CUS ＋ low intensity running group （LIR） and CUS ＋ moderate intensity running group （MIR）. Rats were suffered 4 weeks chronic stress with FLU, low intensity exercise or moderate intensity exercise. The effects of aerobic exercise on depression-like behavior, anxiety-like behavior and cognitive impairment were tested by open field test （ OFT）, sucrose preference test （SP） , novelty-suppressed feeding test （NSF） and novel object recognition experiment （NOR）. The effects of aerobic exercise on serum corticosterone, inflammatory factors IL-1β, levels of GFAP, S100β, p-ERK, p-CREB and BDNF in hippocampus were tested by ELISA and Western blot. These tests were for exploring behavioral effects and mechanisms of aerobic exercise＇s anti-depression. Results ： 1 ） Low intensity exercise and moderate intensity exercise increased the open activities, shorted latent period of novelty-suppressed feeding, and improved recognition index of novel object in rats with chronic stress. 2） Aerobic exercise effectively reversed the abnormal increase of serum corticosterone and decreased the secretion of IL-1 β in the hippocampas of rats with chronic stress. 3） Aerobic exercise decreased the expressions of GFAP and S100β, and increased the expressions of BD- NF, p-ERK and p-CREB that are important in BDNF/ERK/CREB signal transduetion pathway in rats with chronic stress. Conclusions： Aerobic exercise can regulate the abnormal increase of serum eorticosterone, reduce the release of inflammatory factor in the hippoeampus, and improve the activity of GFAP and S100β, which can protect neurons. 2） Aerobic exercise can active CREB, BDNF and ERK, improve the neurotrophie effect, promote the growth of neurons, and increase the plasticity and neurogenesis, which can resist depression.