急性睡眠剥夺调控AMPK-自噬信号致小鼠抑郁样行为机制

Acute sleep deprivation leads to depression-like behavior by modulating AMPK-autophagy signaling

目的研究急性睡眠剥夺(SD)对小鼠焦虑和抑郁样行为的影响,并探讨其可能的分子机制。方法随机将33只雄性8周龄C57BL/6小鼠分为环境对照(EC)组和SD组。采用旷场实验和十字高架实验评估小鼠自主行为和焦虑行为;采用强迫游泳实验和悬尾实验检测小鼠抑郁行为。Western blot法检测小鼠海马区神经炎症蛋白和自噬相关蛋白水平的表达。结果与EC组比较,在旷场实验中SD组小鼠总运动距离显著增加(P<0.01),穿线次数和中央区域时间未表现出显著差异;在强迫游泳实验中SD组小鼠不动时间显著增加(P<0.01),但悬尾实验和十字高架实验中各指标均无显著差异。Western blot结果显示:与EC组比较,SD组小鼠海马区NLRP1、TNF-α、IL-1β、IL-18和自噬蛋白p62水平显著升高,Atg5、Atg7水平显著降低,AMPK磷酸化水平也显著降低。结论SD可能通过抑制小鼠海马区AMPK-自噬信号,上调神经炎症水平,导致小鼠出现抑郁样行为。

Objective This work mainly studied the effects of acute sleep deprivation(SD)on anxiety and depression behavior in mice,and explored possible molecular mechanisms.Methods 33 male 8-week-old C57BL/6 mice were randomly divided into environment control(EC)group and a SD group.The open field test and elevated plus maze test were used to evaluate their spontaneous and anxiety behavior,while the forced swimming test and tail suspension test were used to detect depression behavior in mice.The expression of neuroinflammatory proteins and the levels of autophagy-related proteins were detected by Western blot method.Results Behavioral results showed that comparing to the EC group,the total distance traveled by mice in the SD group significantly increased in the open field test(P<0.01),while the number of crossings and time spent in the central area did not show significant differences.Results from the forced swimming test showed that immobility time significantly increased in the SD group mice(P<0.01),but there were no significant differences in tail suspension and elevated plus maze test.Western blot results showed that comparing to the EC group,the levels of NLRP1,TNF-α,IL-1β,IL-18,and autophagy protein p62 in the hippocampus of the SD group mice significantly increased,while the levels of Atg5,Atg7 decreased significantly,and the phosphorylation level of AMPK also decreased significantly.Conclusion SD may induce depression-like behavior in mice by inhibiting the AMPK-autophagy signaling pathway in the hippocampus and upregulating neuroinflammatory levels.