慢性不可预知应激所致抑郁小鼠性行为受损及VTA脑区BDNF的表达下降

Impaired sexual behavior and decreased expression of BDNF in VTA of depressed mice induced by chronic unpredictable stress

目的研究慢性不可预知应激(CUS)对小鼠性行为的影响及其可能分子机制。方法将20只雄性C57BL/6J小鼠随机均分为Control组和CUS组,并平衡两组间小鼠的体质量,对照组3~5只/笼,正常喂养;CUS组给予21 d CUS结合单笼饲养,建立抑郁模型。21 d后,进行糖水偏好实验和强迫游泳实验验证CUS的效果。通过嗅觉偏好测试和雌鼠尿液嗅实验检测小鼠的性行为,检测小鼠腹侧被盖区(VTA)脑源性神经营养因子(BDNF)蛋白和mRNA的表达。结果CUS导致小鼠糖水偏好降低(P<0.05),强迫游泳不动时间增加(P<0.05)等抑郁样行为,小鼠嗅觉偏好测试中在雌鼠垫料一侧的时间与在雄鼠垫料一侧的时间无差异,雌鼠尿液嗅实验中闻嗅雌鼠尿液的时间减少(P<0.05)等性行为受损,且CUS小鼠VTA脑区BDNF的蛋白表达降低,BDNF总mRNA和ExonⅠ、ExonⅡmRNA表达量下降,差异有统计学意义(P<0.05)。结论CUS致抑郁小鼠性行为受损和VTA脑区BDNF表达下降,表明BDNF信号通路可能参与CUS致小鼠性行为受损的调控。

Objective To study the effect of chronic unpredictable stress(CUS)on the sexual behavior of mice and its possible molecular mechanism.Methods 20 male C57BL/6J mice were divided into two groups randomly:control group(n=10)and CUS group(n=10),and the weight of the mice between the two groups was balanced.The control group was 3-5 mice per cage and normal feeding.CUS group was subjected to 21 days CUS combined with single cage fed to establish a depression model.After 21 days,the depressive-like behaviors of the two groups were tested by sucrose preference test and forced swimming test.Then the sexual behavior was detected by olfactory preference test and female urine sniffing test,and the protein and mRNA expression of brain-derived neurotrophic factor(BDNF)in ventral tegmental area(VTA)were detected.Results CUS could significantly decrease sucrose preference(P<0.05)and increase the immobility time in the forced swim test(P<0.05)compared to control mice,indicating depression-like behavior in mice,and impaired sexual behavior in the olfactory preference test(P<0.05)and female urine sniffing test(P<0.05)in mice,and decreased the expression of BDNF in VTA brain regions.The difference was statistically significant.Conclusion The impaired sexual behavior of mice induced by CUS may be related to the decreased expression of BDNF in VTA brain regions.The BDNF signaling pathway may be involved in the regulation of impaired sexual behavior of mice induced by CUS.