Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness.
Mouse strain differences in the effects of corticotropin releasing hormone (CRH) on sleep and wakefulness.
复制标题
促肾上腺皮质激素释放激素 (CRH) 对睡眠和觉醒影响的小鼠品系差异。
DOI：
10.1016/j.brainres.2007.11.007
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发表时间：
2008
期刊：
影响因子：
2.9
通讯作者：
Tang,X
中科院分区：
文献类型：
--
作者：
Sanford,LD;Yang,L;Wellman,LL;Dong,E;Tang,X
促肾上腺皮质激素释放激素（CRH）在中枢神经系统对应激源的反应中起着重要作用，并与应激诱导的睡眠改变有关。在没有应激源的情况下，CRH有助于自发觉醒的调节。我们研究了CRH和astressin（AST）（一种非特异性CRH拮抗剂）对两种小鼠品系的觉醒和睡眠的影响，这两种小鼠品系对压力的反应不同，以确定CRH是否也可能对不受干扰的睡眠和活动产生差异性影响。向反应性较低的C57 BL/6 J（n=7）和高反应性的BALB/cJ（n=7）雄性小鼠植入用于通过遥测确定睡眠的发射器和瞄准侧脑室的引导套管。从手术中恢复并习惯于处理后，在开灯后第4小时内ICV微量注射CRH（0.04、0.2和0.4 μg）、AST（0.1、0.4和1.0 μg）或单独溶媒（无热原生理盐水，0.2 μl），并记录随后8小时的睡眠。在不同的条件和不同的菌株下进行了觉醒和睡眠的比较。在C57 BL/6 J小鼠中，微量注射CRH（0.2 μg）和CRH（0.4 μg）后REM显著减少，微量注射CRH（0.4 μg）后NREM和总睡眠减少。CRH（0.04 μg）和AST没有显著改变觉醒或睡眠。在BALB/cJ小鼠中，CRH（0.4 μg）增加觉醒，减少NREM、REM和总睡眠。AST在低剂量和高剂量下降低主动觉醒并显著增加REM。这些发现表明，CRH产生唤醒的变化时，给予其他未受干扰的小鼠。CRH和AST作用的品系差异可能与C57 BL/6 J和BALB/cJ小鼠对应激源的相对反应性以及CRH系统的潜在差异有关。
Corticotropin releasing hormone (CRH) plays a major role in central nervous system responses to stressors and has been implicated in stress-induced alterations in sleep. In the absence of stressors, CRH contributes to the regulation of spontaneous waking. We examined the effects of CRH and astressin (AST), a non-specific CRH antagonist, on wakefulness and sleep in two mouse strains with differential responsiveness to stress to determine whether CRH might also differentially affect undisturbed sleep and activity. Less reactive C57BL/6J (n=7) and high reactive BALB/cJ (n=7) male mice were implanted with a transmitter for determining sleep via telemetry and with a guide cannula aimed into a lateral ventricle. After recovery from surgery and habituation to handling, ICV microinjections of CRH (0.04, 0.2, and 0.4 μg), AST (0.1, 0.4, and 1.0 μg) or vehicle alone (pyrogen-free saline, 0.2 μl) were administered during the fourth hour after lights on and sleep was recorded for the subsequent 8 h. Comparisons of wakefulness and sleep were conducted across conditions and across strains. In C57BL/6J mice, REM was significantly decreased after microinjections of CRH (0.2 μg) and CRH (0.4 μg), and NREM and total sleep were decreased after microinjections of CRH (0.4 μg ). CRH (0.04 μg) and AST did not significantly change wakefulness or sleep. In BALB/cJ mice, CRH (0.4 μg) increased wakefulness and decreased NREM, REM and total sleep. AST decreased active wakefulness and significantly increased REM at the low and high dosages. These findings demonstrate that CRH produces changes in arousal when given to otherwise undisturbed mice. Strain differences in the effects of CRH and AST may be linked to the relative responsiveness of C57BL/6J and BALB/cJ mice to stressors and to underlying differences in the CRH system.