Iijima Michihiko, Nikaido Takato, Akiyama Masashi, Moriya Takahiro, Shibata Shigenobu
Department of Pharmacology and Brain Science, School of Human Sciences, Waseda, University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan.
Eur J Neurosci. 2002 Sep;16(5):921-9. doi: 10.1046/j.1460-9568.2002.02140.x.
While the suprachiasmatic nucleus (SCN) coordinates the majority of daily rhythms, some circadian patterns of expression are controlled from outside of the SCN. These include responses to daily methamphetamine (MAP) injection, or daily restricted feeding. The mechanisms underlying these SCN-independent circadian rhythms are unknown. A circadian oscillation in the expression of mPer1 and/or mPer2, mouse period, in the SCN is considered necessary to generate an SCN-dependent circadian rhythm. Therefore, in this experiment, we examined the association between mPer gene expression and the MAP-induced, SCN-independent circadian rhythm. Acute injection of MAP caused an elevation of mPer1, mBmal1, and mNpas2 gene expression in the striatum and mPer1 in the liver. Daily MAP injection at a fixed time for 6 days shifted the rhythmic mPer1 and mPer2 expression in the striatum from a nocturnal to a diurnal rhythm, but failed to affect that in the SCN. Although lesion of the SCN 'flattened'mPer gene oscillation in the striatum and liver, daily MAP injection caused both behavioural and mPer gene expression rhythms. Daily MAP injection at variable injection intervals (12-36 h) for 6 days, however, failed to produce mPer gene rhythm in the striatum. Daily repeated MAP signals may strengthen the oscillatory force of SCN-independent circadian behavioural and molecular rhythms. The present results suggest that daily oscillation of mPer genes outside the SCN is closely associated with the regulation of SCN-independent rhythms. Thus, the present experiment highlights strongly the important role of clock gene expression, in the brain, that underlies the circadian behavioural rhythm.
虽然视交叉上核(SCN)协调着大部分日常节律,但一些昼夜节律性的表达模式是由SCN之外的因素控制的。这些包括对每日注射甲基苯丙胺(MAP)或每日限时进食的反应。这些独立于SCN的昼夜节律背后的机制尚不清楚。SCN中mPer1和/或mPer2(小鼠周期基因)表达的昼夜振荡被认为是产生依赖于SCN的昼夜节律所必需的。因此,在本实验中,我们研究了mPer基因表达与MAP诱导的、独立于SCN的昼夜节律之间的关联。急性注射MAP导致纹状体中mPer1、mBmal1和mNpas2基因表达以及肝脏中mPer1表达升高。在固定时间每日注射MAP持续6天,使纹状体中节律性的mPer1和mPer2表达从夜间节律转变为白天节律,但未能影响SCN中的表达。虽然损毁SCN会使纹状体和肝脏中mPer基因振荡“变平”,但每日注射MAP仍会引起行为和mPer基因表达节律。然而,以可变注射间隔(12 - 36小时)每日注射MAP持续6天,未能在纹状体中产生mPer基因节律。每日重复的MAP信号可能会增强独立于SCN的昼夜行为和分子节律的振荡力量。目前的结果表明,SCN之外的mPer基因的每日振荡与独立于SCN的节律调节密切相关。因此,本实验强烈凸显了大脑中时钟基因表达在昼夜行为节律背后的重要作用。