自愿转轮运动对慢性应激大鼠焦虑及抑郁样行为、前额叶皮质炎症因子及NGF/TrkA信号通路的影响

Effects of Voluntary Wheeling on Anxiety,Depression-Like Behaviours,Inflammation and NGF/TrkA Pathway in the Prefrontal Cortex of Chronic Stress Rats

目的:通过测量自愿转轮运动对慢性不可预知应激(CUS)大鼠前额叶皮质(PFC)炎症因子(IL-6、TNF-a及IL-10)水平及NGF和TrkA表达的变化,探讨自愿转轮运动改善CUS大鼠焦虑及抑郁样行为的可能机制。方法:将44只大鼠随机分为安静对照组(C)、运动组(E)、慢性应激组(CUS)和应激运动组(CUS+E)。随后,CUS组及CUS+E组大鼠建立CUS抑郁模型,同时,E组及CUS+E组大鼠进行4周自愿转轮运动。自愿运动及应激结束后,采用高架迷宫(EPM)及开场实验(OFT)评估大鼠焦虑及抑郁样行为;除外,PFC炎症因子和NGF及TrkA表达被测量。结果:(1)与C组比较,EPM实验中CUS组大鼠OE%(P<0.01)和OA%减少(P<0.05),焦虑指数增加(P<0.05);OFT实验中,中央格时间(P<0.05)及粪便颗粒(P<0.01)均显著增多,跨格次数减少(P<0.01);PFC促炎因子IL-6及TNF-a水平增加(P<0.01),抗炎因子IL-10水平下降(P<0.01),NGF及TrkA表达均显著降低(P<0.01)。(2)4周自愿转轮运动显著削弱了大鼠焦虑及抑郁样行为;PFC促炎因子TNF-a水平下降(P<0.05),抗炎因子IL-10水平增加(P<0.05),而IL-6水平无显著改变(P>0.05);PFC NGF及Trk A表达均增强(P<0.05,P<0.01)。结论:自愿转轮运动可削弱CUS大鼠焦虑及抑郁样行为,可能与此运动增强PFC抗炎能力激活NGF-TrkA信号通路,从而纠正CUS诱导的PFC功能紊乱起到脑保护作用有关。

Objective:To examine the impact of voluntary wheeling on CUS induced anxiety and depressive-like behavior and possible mechanism by measuring PFC inflammatory biomarkers levels(IL-6,TNF-a and IL-10)and NGF and TrkA expression. Methods:44 rats were randomly allocated into the following subgroups:the sedentary control group(C),the exercise group(E),chronic unpredictable stress group(CUS)and exercised+CUS group(CUS+E).CUS and CUE+E group rats are exposed CUS and E and CUS+E group rats received 4-week voluntary wheeling exercise at the same time. Thereafter,the anxiety and depressive behavioral changes were assessed by elevated-plus maze(EPM)and open field test(OFT).Additionally,the PFC inflammatory biomarkers and NGF,TrkA expression were measured. Results:1)Compared to the C group rats,OA(time spent in the open arm)%,OE(open arm entries)%decreased,anxiety index increased(P<0.05,P<0.01)in the EPM test;crossing numbers decreased(P<0.01),time spent in the centre and fecal particles increased(P<0.05,P<0.01)in the CUS group rats;TNF-α and IL-6 levels increased and IL-10 level decreased(P<0.01 respectively)and NGF,TrkA expression significantly decreased in PFC(P<0.01)in CUS group rats when compared to the C group.Moreover,4 weeks of voluntary exercise treatment significantly improved anxiety and depressive like behavior caused by CUS;meanwhile,exercise training significantly decrease TNF-α level and increase IL-10 level in PFC(P<0.05 respectively),while the IL-6 level in PFC was not significant difference(P>0.05);moreover,NGF and TrkA expression in PFC significantly enhanced after exercise treatment(P<0.05,P<0.01).Conclusions:That long-term voluntary exercise appears to result in alleviated anxiety-depressive related behaviour. Its possible mechanism might be that voluntary exercise prevents PFC neuroinflammation responses and activates NGF/TrkA pathway which reverse the PFC dysfunction induced by CUS and protect the PFC against the deleterious effects of chronic stress.