FEEDING-ELICITED CATAPLEXY IN OREXIN KNOCKOUT MICE
FEEDING-ELICITED CATAPLEXY IN OREXIN KNOCKOUT MICE
复制标题
DOI：
10.1016/j.neuroscience.2009.04.007
复制
发表时间：
2009-07-21
期刊：
影响因子：
3.3
通讯作者：
Mochizuki, T.
中科院分区：
文献类型：
--
作者：
Clark, E. L.;Baumann, C. R.;Mochizuki, T.
缺乏食欲素/下丘脑泌素信号传导的小鼠在主动觉醒期间会突然发生肌张力不足和瘫痪。这些事件非常类似于癫痫，发作性睡病患者由强烈的积极情绪引发的突然肌肉无力发作，但目前尚不清楚小鼠癫痫是否由积极情绪引发。为了确定积极的情绪是否会引起小鼠catabolism，我们将orexin敲除（KO）小鼠置于定期或高度可口的食物喂养方案中。基线睡眠/觉醒行为记录为随意进食常规食物。然后将小鼠置于预定的喂养方案中，在接下来的10天中，它们在黑暗开始后3小时接受其正常量的食物的60%。野生型和KO小鼠迅速进入常规食物的计划喂养，在喂养时间之前具有更多的觉醒和运动活动。在计划喂养的第10天，食欲素KO小鼠在食物预期期具有略微更多的cataerance，并且在黑暗期的后半段具有更多的cataerance，此时它们可能正在搜寻剩余的食物。为了测试更可口的食物是否会增加catabolism，小鼠然后被切换到计划喂养等热量的Froot Loops，一种经常在行为研究中用作奖励的食物。有了这种非常可口的食物，食欲素基因敲除小鼠在食物预期期和整个黑暗期有更多的症状。定期喂食，尤其是食用美味食物，会导致小鼠突然倒地的增加，这表明积极的情绪可能会引发小鼠突然倒地，就像发作性睡病患者一样。建立这种联系有助于验证orexin KO小鼠作为人类嗜睡症的优秀模型，并提供了一个更好地了解触发cataepsy的机制的机会。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Mice lacking orexin/hypocretin signaling have sudden episodes of atonia and paralysis during active wakefulness. These events strongly resemble cataplexy, episodes of sudden muscle weakness triggered by strong positive emotions in people with narcolepsy, but it remains unknown whether murine cataplexy is triggered by positive emotions. To determine whether positive emotions elicit murine cataplexy, we placed orexin knockout (KO) mice on a scheduled feeding protocol with regular or highly palatable food. Baseline sleep/wake behavior was recorded with ad libitum regular chow. Mice were then placed on a scheduled feeding protocol in which they received 60% of their normal amount of chow 3 h after dark onset for the next 10 days. Wild-type and KO mice rapidly entrained to scheduled feeding with regular chow, with more wake and locomotor activity prior to the feeding time. On day 10 of scheduled feeding, orexin KO mice had slightly more cataplexy during the food-anticipation period and more cataplexy in the second half of the dark period, when they may have been foraging for residual food. To test whether more palatable food increases cataplexy, mice were then switched to scheduled feeding with an isocaloric amount of Froot Loops, a food often used as a reward in behavioral studies. With this highly palatable food, orexin KO mice had much more cataplexy during the food-anticipation period and throughout the dark period. The increase in cataplexy with scheduled feeding, especially with highly palatable food, suggests that positive emotions may trigger cataplexy in mice, just as in people with narcolepsy. Establishing this connection helps validate orexin KO mice as an excellent model of human narcolepsy and provides an opportunity to better understand the mechanisms that trigger cataplexy. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.