Adrb1-A187V突变短睡眠小鼠在不同饮食条件下的行为变化

Behavioral changes of transgenic mice carrying Adrb1-A187V mutation with short sleep duration under different dietary conditions

目的探究在限制性饮食和高脂饮食模式下,短睡眠Adrb1-A187V小鼠模型与其野生型小鼠行为活动的差异。方法将短睡眠基因小鼠分为常规饮食组、气味保留禁食组、完全禁食组、高脂饮食组。常规饮食组:小鼠代谢与行为监测系统中,Adrb1^(+/+)小鼠25只和Adrb1^(+/m)小鼠26只。气味保留禁食组:小鼠代谢与行为监测系统中,Adrb1^(+/+)小鼠17只,Adrb1^(+/m)小鼠19只;EEG/EMG睡眠活动监测系统中,Adrb1^(+/+)小鼠6只,Adrb1^(+/m)小鼠6只。完全禁食组:小鼠代谢与行为监测系统中,Adrb1^(+/+)小鼠6只,Adrb1^(+/m)小鼠4~5只;EEG/EMG睡眠活动监测系统中,Adrb1^(+/+)小鼠6只,Adrb1^(+/m)小鼠6只。高脂饮食组:小鼠代谢与行为监测系统中,Adrb1^(+/+)小鼠6只,Adrb1^(+/m)小鼠7只;EEG/EMG睡眠活动监测系统中,Adrb1^(+/+)小鼠6只,Adrb1^(+/m)小鼠6只。在两组小鼠颅骨上植入脑电/肌电电极,通过给予小鼠24 h气味保留禁食实验、完全禁食实验以及高脂饮食实验,检测其在不同进食模式下,小鼠如何改变行为活动以适应饮食环境的变化。结果在气味保留禁食实验中,Adrb1^(+/m)小鼠表现出更加稳定的运动水平的波动,活动相对较少(P<0.05),睡眠时间更长(P<0.01,P<0.05),有利于适应饥饿环境,具有更耐饿的特性;完全禁食实验中,Adrb1^(+/m)小鼠的夜间进水量更多(P<0.05),进水的生物节律性更好,表现出在进水方面出现的“少食多餐”。同时,非快速动眼睡眠(NREM)时长增加(P<0.01),可以帮助小鼠抵抗饥饿。高脂饮食实验中,Adrb1^(+/m)小鼠表现出更高的运动水平,表现为夜间站立次数和运动距离水平更高(P<0.0001),且快速动眼睡眠(REM)在白天增加(P<0.01)。结论Adrb1-A187V突变小鼠可更快速对环境变化做出反应,在限制性饮食条件中,通过增加睡眠减少能量消耗以维持能量稳态;在高脂饮食条件中,则保持更高的运动水平,与限制性饮食条件相反。

Objective To observe the effects of restricted and high-fat diets on behavioral changes of wild-type(Adrb1^(+/+))and transgenic mice carrying Adrb1-A187V mutation(Adrb1^(+/m))with short sleep durations.Methods Adrb1^(+/+)and Adrb1^(+/m) C57BL/6 mice were randomized into normal chow group(25 Adrb1^(+/+)and 26 Adrb1^(+/m) mice for behavioral monitoring),odor retention fasting group(17 Adrb1^(+/+)and 19 Adrb1^(+/m) mice for behavioral monitoring;6 Adrb1^(+/+)mice and 6 Adrb1^(+/m) mice for EEG/EMG monitoring),absolute fasting group(6 Adrb1^(+/+)and 4-5 Adrb1^(+/m) mice for behavioral monitoring;6 Adrb1^(+/+)and 6 Adrb1^(+/m) mice for EEG/EMG monitoring),and high-fat diet group(6 Adrb1^(+/+)and 7 Adrb1^(+/m) mice for behavioral monitoring;6 Adrb1^(+/+)and 6 Adrb1^(+/m) mice for EEG/EMG monitoring).Electrodes for EEG and muscle activity monitoring were implanted on the skulls of the mice.After 24 h of odor retention fasting,absolute fasting,or high-fat feeding,the mice were observed for behavioral changes adapted to diet changes.Results In odor retention fasting experiment,Adrb1^(+/m) mice exhibited more stable fluctuations of activities with mildly reduced movement and prolonged sleep duration,indicating enhanced starvation resistance.In absolute fasting experiment,Adrb1^(+/m) mice showed significantly increased nighttime water intake,improved rhythmicity in water intake(frequent intakes in small amounts),and increased duration of non-rapid eye movement sleep(NREM).In the high-fat diet experiment,Adrb1^(+/m) mice showed higher levels of activity with increased instances of nighttime rearing,longer movement distances,and increased rapid eye movement sleep during daytime.Conclusion Adrb1^(+/m) mice can quickly respond to environmental changes and under restricted dietary conditions,they can conserve energy by increasing sleep to maintain energy homeostasis but show higher levels of activity under high-fat dietary conditions.