运动疲劳通过P物质诱导的小胶质细胞活化引发大鼠抑郁样行为  

Exercise fatigue triggers depressive-like behaviour in rats viasubstance P-induced microglia activation

作　　者：苏畅 许子萱 金硕 杨倩芸 席超[3] 孙丽娜[1,4] SU Chang;XU Zixuan;JIN Shuo;YANG Qianyun;XI Chao;SUN Lina(College of P.E and Sports,Beijing Normal University,Beijing 100875;Beijing Sanfan Middle School,Beijing 100088;College of life sciences,Beijing Normal University,Beijing 100875;State Key Laboratory of Cognitive Neuroscience and Learning,Beijing Normal University,Beijing 100875,China)

机构地区：[1]北京师范大学体育与运动学院,北京100875 [2]北京市三帆中学,北京100088 [3]北京师范大学生命科学学院,北京100875 [4]北京师范大学认知神经科学与学习国家重点实验室,北京100875

出　　处：《神经解剖学杂志》2024年第6期688-694,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(32000835);中国教育学会“第六批体育与卫生(国防教育)”专项课题(202300201312ZXB);北京师范大学认知神经科学与学习国家重点实验室开放课题(CNLZD2104)。

摘　　要：目的:探究运动疲劳导致大鼠抑郁样行为的中枢调控机制。方法:将雄性SD大鼠随机分为对照组(Control)和疲劳组(Fatigue)。运动疲劳模型的构建采用3级递增负荷跑台训练方案。利用糖水偏好实验评价大鼠的抑郁样行为,行为学测试结束后使用免疫组织化学染色观察大鼠海马CA1区的P物质(SP)表达情况以及小胶质细胞(MG)激活水平,并用Western Blot检测海马p38丝裂原活化蛋白激酶(p38 MAPK)磷酸化水平(p-p38/p38)的变化。结果:糖水偏好实验发现,疲劳组大鼠的糖水偏好率明显低于对照组(P<0.01);免疫组织化学染色显示,疲劳组大鼠海马CA1区的SP表达水平与对照组相比显著增加(P<0.01),并伴随海马CA1区MG活化程度的显著升高(P<0.05)。Western Blot结果显示,运动疲劳可导致大鼠海马p-p38 MAPK/p38 MAPK值明显增加(P<0.01)。结论:运动疲劳引发抑郁情绪的产生与海马CA1区SP分泌上调以及MG过度活化有关,p38 MAPK通路的激活可能是运动疲劳导致不良情绪的调控机制。Objective:To investigate the central regulatory mechanisms underlying depression-like behavior induced by exercise fatigue in rats.Methods:Male Sprague-Dawley(SD)rats were randomly divided into a control group and a fatigue group.The exercise-induced fatigue model was established by a three-level incremental load treadmill training protocol.The sucrose preference test(SPT)was conducted to evaluate depressive-like behavior in the rats.Following the behavioral testing,Immunohistochemical staining was used to observe the expression of substance P(SP)and the activation level of microglia(MG)in the CA1 region of the hippocampus.Additionally,Western Blot were performed to observe the hippocampal phosphorylation level of p38 mitogen-activated protein kinase(p38 MAPK).Results:The SPT revealed that the sucrose preference rate of rats in the fatigue group was significantly lower than that of the control group(P<0.01);Immunohistochemical staining showed that the expression level of SP in the hippocampal CA1 region of rats in the fatigue group was significantly increased compared with that of the control group(P<0.01),and accompanied by a significant increase in the activation level of MG in the hippocampal CA1(P<0.05).In addition,Western Blot results indicated that exercise-induced fatigue led to a significant increase in the p-p38 MAPK/p38 MAPK values in the hippocampus of rats(P<0.01).Conclusion:The development of depressive-like behavior induced by exercise-induced fatigue is associated with upregulated SP secretion and excessive MG activation in the hippocampal CA1 region.The activation of the p38 MAPK pathway may be a regulatory mechanism underlying the adverse mood states caused by exercise-induced fatigue.

关 键 词：运动疲劳 P物质 小胶质细胞 p38 MAPK 抑郁样行为 大鼠 

分 类 号：R749.4[医药卫生—神经病学与精神病学]