运动通过下丘脑室旁核CRH神经元改善慢性束缚压力应激诱导的焦虑样行为  

Exercise Ameliorates Chronic Restraint Stress-induced Anxiety via PVN CRH Neurons

作　　者：陈静[1,2] 陈聪聪 张凯娜 赖昱霖 邹杨 CHEN Jing;CHEN Cong-Cong;ZHANG Kai-Na;LAI Yu-Lin;ZOU Yang(Department of Neurosurgery,Xuanwu Hospital,China International Neuroscience Institute,Capital Medical University,Beijing 100053,China;School of Sport Science,Laboratory of Sports Stress and Adaptation of General Administration of Sport,Beijing Sport University,Beijing 100084,China;China Volleyball College,Beijing Sport University,Beijing 100084,China)

机构地区：[1]首都医科大学宣武医院神经外科,中国国际神经科学研究所,北京100053 [2]北京体育大学运动人体科学学院,国家体育总局运动应激适应重点实验室,北京100084 [3]北京体育大学中国排球运动学院,北京100084

出　　处：《生物化学与生物物理进展》2025年第2期501-512,共12页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(32100821);中央高校基本科研业务经费专项(2021QN030)资助项目。

摘　　要：目的探讨下丘脑室旁核(paraventricularnucleus,PVN)促肾上腺皮质激素释放素(corticotropin releasing hormone,CRH)神经元在慢性束缚压力应激(chronic restraint stress,CRS)诱导焦虑样行为中的作用,以及运动干预是否通过PVN CRH神经元缓解慢性束缚压力应激诱导的焦虑样行为。方法20只8周龄雄性C57BL/6J小鼠,随机分为空白对照(control,Ctrl)组和CRS组,并通过旷场(open field test,OFT)和高架十字迷宫(elevated plus maze test,EPM)范式,评估其焦虑样行为,并对慢性束缚压力应激后的小鼠摄食量进行统计。通过免疫荧光染色的方法观察PVN脑区c-Fos的表达情况,以及与CRH神经元的共标情况。利用化学遗传学激活PVN CRH神经元,检测其焦虑情况。通过8周跑台干预(10~16 m/min,60 min/d,6 d/周),观察其对慢性束缚压力应激诱导的焦虑样行为的改善作用。最后,探讨PVN CRH神经元在运动改善焦虑样行为中的作用机制。结果与Ctrl组相比,CRS组小鼠出现明显的焦虑样行为,在旷场中间区域的时间减少(P<0.001),在高架十字迷宫的开臂时间减少(P<0.001),并且出现食欲下降的现象(P<0.05);与Ctrl组相比,CRS组小鼠能够促进PVN脑区c-Fos的表达(P<0.001),并且这些c-Fos信号与CRH神经元有大量共标(P<0.001);利用化学遗传学直接激活PVN CRH神经元,小鼠出现焦虑样行为(P<0.05),并且出现抑制摄食的现象;运动干预可以缓解CRS诱导的焦虑样行为(P<0.001),并缓解摄食抑制现象(P<0.05);运动干预可以抑制由CRS诱导的PVN CRH神经元活性增强(P<0.001),并且消融PVN CRH神经元可缓解CRS诱导产生的焦虑样行为。结论慢性束缚压力应激通过激活PVN CRN神经元,诱导小鼠产生焦虑样行为和食欲下降的现象;8周运动干预可能通过抑制PVN CRH神经元缓解慢性束缚压力应激诱导的焦虑样行为;CRH PVN神经元损毁,慢性束缚压力所诱导的焦虑样行为得到改善。这一研究结果揭示了运动缓解�Objective To investigate the role of paraventricular nucleus(PVN)corticotropin releasing hormone(CRH)neurons in chronic restraint stress(CRS)-induced anxiety-like behavior.And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons.Methods Twenty 8-week-old male C57BL/6J mice were randomly divided into control(Ctrl)group and chronic restraint stress(CRS)group.The open field test(OFT)and elevated plus maze(EPM)were used to evaluate anxiety-like behavior of the mice.Food intake was recorded after CRS.Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons.We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior.8-week treadmill training(10-16 m/min,60 min/d,6 d/week)were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it.Results Compared with Ctrl group,CRS group exhibited significant anxiety-like behavior.In OFT,the mice in CRS groups spent less time in center area(P<0.001).In EPM,the time in open arm in CRS group were significantly decreased(P<0.001).Besides,food intake was also suppressed in CRS group compared with Ctrl group(P<0.05).Compared with Ctrl group,CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos(P<0.001).Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior(P<0.05)and inhibited feeding behavior(P<0.01).Exercise relieves chronic restraint stress-induced anxiety(P<0.001)and relieved the anorexia caused by chronic restraint stress(P<0.05).Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons(P<0.001).Furthermore,ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior.Conclusion CRS activated PVN CRH neurons,induced anxiety-like behavior and reduced food intake.8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron.Ablation of CRH PVN neurons ameliorate

关 键 词：慢性束缚压力 焦虑样行为 PVN CRH神经元 运动 

分 类 号：Q42[生物学—神经生物学] R87[生物学—生理学]