运动疲劳损害大鼠空间认知能力并导致海马CA1区L-LTP抑制

Exercise-induced chronic fatigue impairs spatial cognition of rats and causes L-LTP inhibition in hippocampal CA1 region

目的:探讨运动疲劳对空间认知能力的影响及海马突触可塑性调控机制。方法:采用随机数字法将雄性SD大鼠分为对照组(control)和疲劳组(fatigue),选用3级递增负荷跑台训练方案,建立慢性力竭运动疲劳模型。利用Y迷宫空间识别记忆实验评估大鼠的空间识别和记忆变化,使用Western Blot测定海马组织cAMP反应元件结合蛋白(CREB)表达及磷酸化水平,并利用在体电生理记录大鼠海马CA1区晚期时相长时程增强效应(L-LTP),随后通过免疫组织化学染色观察大鼠海马CA1区小清蛋白(PV)的表达。结果:疲劳组大鼠在新异臂的停留时间比和在各臂的总穿梭次数均明显低于对照组(P<0.01)。高频刺激后30、60、120直至180 min,疲劳组大鼠海马CA1区场兴奋性突触后电位(fEPSP)斜率较对照组大鼠均显著降低(P<0.01)。Western Blot结果表明,疲劳组大鼠海马组织磷酸化CREB(p-CREB)水平明显低于对照组(P<0.05)。免疫组织化学染色显示,疲劳组大鼠海马CA1区PV表达下调(P<0.05)。结论:运动疲劳可导致大鼠空间认知能力受损,其机制可能与海马L-LTP抑制、CREB磷酸化水平降低以及PV阳性神经元减少有关。

Objective:To investigate the effects of motor fatigue on spatial cognitive ability and the mechanism of hippocampal synaptic plasticity regulation.Methods:Male SD rats were divided into control group and fatigue group using random number method.A three-stage incremental load running plaform training protocol was selected to establish a chronic exhaustion exercise-induced fatigue rat model.The Y-maze spatial recognition memory experiment was used to assess the changes of spatial recognition and memory.The expression and phosphorylation of cAMP-responsive element binding protein(CREB)and in hippocampal tissues were measured by Western Blot.The late-phase long-term potentiation(L-LTP)in hippocampal CAl region of rats was recorded in vivo electrophysiological recording.Parvalbumin(PV)expression in the rat hippocampal CAl was subsequently detected by immunohistochemical staining.Results:The time in novel arm and the novel arm entries of rats in the fatigue group were significantly lower than those in the control group(P<0.01).The slope of fEPSP was significantly lower in the fatigue group than that of control group at 30 min,60 min,120 min and up to 180 min after high-frequency stimulation(P<0.01).Western Blot results showed that the expression and phosphorylated CREB in rat hippocampal tissue of fatigue group was significantly lower than that of control group(P<0.05).Immunohistochemical staining showed that the PV positive neurons and fibers in hippocampal CA1 region of rats of fatigue group was obviously Less than those of control group(P<0.05).Conclusion:Exercise fatigue can lead to spatial cognitive impairment in rats,and the mechanism may be related to L-LTP inhibition in hippocampus,decreased CREB phosphorylation level,and decreased PV-positive neurons.