急性应激对小鼠焦虑样和抑郁样行为及皮层脑电活动的影响OA
Effect of acute stress on anxiety-like and depression-like behav-iors and cortical electroencephalographic activity in mice
目的 探究急性应激对小鼠焦虑样和抑郁样行为的影响,并表征急性应激后早期阶段皮层脑电信号的变化特征.方法 ① 将成年C57BL/6J雄性小鼠随机分为对照组和应激组.应激组水浸束缚应激(WIRS)2 h,对照组同期禁食不禁水.应激处理后,动物经擦干并于暖光灯下恢复体温30 min后,通过旷场实验和高架十字迷宫实验评估小鼠自发活动、探索行为及焦虑样行为;悬尾实验和强迫游泳实验评估小鼠抑郁样行为;转棒实验评估小鼠运动功能.② 将小鼠随机分为对照组和应激组,应激处理及体温恢复同①,ELISA检测小鼠急性应激结束后0、30、60和180 min时血清皮质酮(CORT)水平.③ 于实验前10天为小鼠植入16通道柔性电极,恢复7d并适应记录环境3 d.适应后将小鼠随机分为对照组和应激组,应激处理及体温恢复同①,在体电生理实验检测皮层脑电活动,分析各频段功率谱密度(PSD).结果 ① 应激组与对照组小鼠的体温、旷场实验的平均运动速度、转棒实验的坠落速度及坠落潜伏期无差异.与对照组相比,应激组小鼠旷场实验的中央区域停留时间百分比、中央区域进入次数、总运动距离、高架十字迷宫实验的开放臂停留时间百分比及开放臂进入次数显著降低,悬尾实验及强迫游泳实验的不动时间显著延长.② 应激组小鼠血清CORT水平在应激后30、60和180 min均显著高于同时期对照组.③ 与对照组相比,应激组小鼠左侧尾内侧内嗅皮层(L-CEnt)高β及低γ频段的PSD显著升高,左侧次级听觉皮层背侧区(L-AuD)全频段PSD显著降低,左侧前额叶联合皮层(L-FrA)50~170 Hz γ频段PSD显著降低,右侧前额叶联合皮层(R-FrA)150~200 Hz γ频段PSD显著升高.结论 WIRS可诱发小鼠焦虑样与抑郁样行为,并伴随血清CORT水平升高及L-CEnt、L-AuD、L-FrA和R-FrA神经振荡的特异性改变.
OBJECTIVE To investigate the effects of acute stress on anxiety-and depression-like behaviors in mice and characterize changes in cortical electroencephalographic activity during the early phase after acute stress exposure.METHODS ① Adult male C57BL/6J mice were randomly assigned to a control group and stress group.The stress group received a single 2 h water immersion restraint stress(WIRS)while the control group fasted but was allowed water access during the same period.After stress treatment,mice were dried and allowed to restore their body temperature under a warm lamp for 30 min.The open field test and elevated plus maze were used to assess spontaneous locomo-tion,exploratory behavior,and anxiety-like behavior.The tail suspension test and forced swim test were conducted to evaluate depression-like behavior.The rotarod test was performed to assess motor function.② Mice were randomly divided into control and stress groups,with stress and recovery proce-dures identical to ①.Serum corticosterone(CORT)levels were measured by ELISA at 0,30,60,and 180 min after stress.③ A 16-channel flexible electrode array was implanted 10 days before experi-ments.After 7 days of postoperative recovery and 3 days of habituation to the recording environment,mice were randomly assigned to control and stress groups.Stress and recovery protocols followed ①.In vivo electrophysiology was conducted to monitor cortical electroencephalographic activity,and power spectral density(PSD)was analyzed across frequency bands.RESULTS ① No differences were observed between the stress and control groups in body temperature,mean velocity,falling speed,or latency to fall.Compared with the control group,significantly reduced time spent in the center,fewer entries into the center,decreased total distance travelled,less time spent in the open arms,fewer open-arm entries,and significantly prolonged immobility times in both the tail suspension test and forced swim test were observed among the stress mice.② Biochemical results showed that serum CORT levels in the stress group were significantly higher than those of controls at 30,60,and 180 min post-stress,but not at 0 minute.③ Electrophysiological data revealed that,compared with control group,the stress group displayed significantly increased PSD in the high-beta and low-gamma bands in the left caudomedial entorhinal cortex(L-CEnt),significantly decreased PSD across all frequency bands in the left secondary auditory cortex dorsal region(L-AuD),significantly reduced PSD in the 50-170 Hz gamma band in the left prefrontal association cortex(L-FrA),and significantly elevated PSD in the 150-200 Hz gamma band in the right prefrontal association cortex(R-FrA).CONCLUSION WIRS can induce anxiety-and depression-like behaviors in mice,accompanied by elevated serum CORT levels and specific alter-ations in neural oscillations in the L-CEnt,L-AuD,L-FrA,and R-FrA.
李波;董婷;苏瑞斌;刘晓燕;张树卓
青岛大学药学院,山东 青岛 266071||军事医学研究院,北京 100850||国家安全特需药品全国重点实验室,北京 100039军事医学研究院,北京 100850||国家安全特需药品全国重点实验室,北京 100039||沈阳药科大学临床药学院,辽宁 沈阳 110016军事医学研究院,北京 100850||国家安全特需药品全国重点实验室,北京 100039军事医学研究院,北京 100850||国家安全特需药品全国重点实验室,北京 100039军事医学研究院,北京 100850||国家安全特需药品全国重点实验室,北京 100039
医药卫生
急性应激水浸束缚应激神经振荡焦虑抑郁皮质酮
acute stresswater immersion restraint stressneural oscillationsanxietydepressioncorticosterone
《中国药理学与毒理学杂志》 2026 (3)
196-206,11
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