2005-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/677626摘要：先前我們的研究成果發現當kindling誘發大白鼠的癲癇發生在不同的時間會對老鼠的睡眠產生不同的影響。當老鼠被控制且適應於12小時燈亮:12小時燈暗的環境後，我們發現在黑暗期(也就是老鼠的活動期)產生的癲癇會增加睡眠(slow wave sleep; SWS)、減少清醒時間(wakefulness)，而若癲癇發生在燈亮期(也就是老鼠的休息期)則會有相反的結果--- 增加清醒時間(wakefulness)、減少睡眠時間(SWS)。而我們亦發現癲癇在黑暗期對睡眠增加的作用主要是透過在腦部所增加的interleukin-1(IL-1) 產生的影響所致。而癲癇發生在燈亮期對睡眠的減少主要則是透過在腦部所增加的corticotropin-releasing hormone (CRH) 所致。目前已知basal forebrain 中的nucleus basalis of Meynert (NBM)可以同時影響睡眠及清醒機制，且它接受來自central nucleus of amygdala的傳入纖維，因此在central nucleus of amygdala給予kindling刺激後有可能改<br> Abstract: Our previous results found that kindling amygdala in different times of circadian rhythm produces diverse patterns in sleep disruption. We determined the alteration of sleep-wake activity in amygdala-kindled rats, occurred at either the beginning of the light period (light-onset kindling) or at the beginning of the dark period (dark-onset kindling). We found that amygdala kindling induced diverse effects on sleep. Slow wave sleep (SWS) and rapid eye movement sleep (REMS) decreased during the first 12-h light period when rats were kindled at light onset. When dark-onset kindling was given, SWS increased but REMS was not altered during the first 12-h dark period. After light-onset kindling circulating corticosterone concentrations increased, and were blocked by intracerebroventricular (ICV) administration of CRH receptor antagonist, astressin or alpha-hCRH. ICV administration of CRH antagonist blocked the light-onset kindling-induced decrease of SWS in a dose-dependent manner. After dark-onset kindling, IL-1 mRNA expression in hippocampus and cortex increased. The dark-onset kindling-induced SWS was blocked in a dose-dependent manner by ICV administration of IL-1 receptor antagonist (IL-1 ra). Slow wave activities (SWAs) during SWS were enhanced regardless of when kindling occurred, but both CRH antagonists and IL-1 ra had little effect on the alteration of SWA. These observations argue that amygdala kindling induced sleep-wake alterations are modulated by central increases in CRH or IL-1. The action sites in brain and the cellular mechanisms of CRH and IL-1 on sleep alterations will be examined in this proposal. Nucleus basalis of Meynert (NBM) in basal forebrain has been implicated in sleep-wake regulation, in which several sleep and wake generator systems (i.e., GABAergic, cholinergic and glutaminergic neurons) composed. GABAergic and partial cholinergic neurons are involved in sleep mechanism whereas glutaminergic and cholinergic neurons have been implicated in wakefulness. In addition, NBM receives afferents from central nucleus of amygdala; therefore the neuronal or synaptic properties in NBM may be altered after kindling stimulation. Based upon on previous suspicion, the effects of CRH and IL-1 on GABAA receptor-mediated current, nicotinic cholinergic receptor-mediated current, NMDA current and AMPA receptor mediated current after amygdala kindling will be examined pharmacologically by whole cell patch clamp recording. We expect this result would provide detail cellular mechanisms of CRH and IL-1on sleep regulation after epilepsy.CRHIL-1amygdalakindlingnucleus basalis of MeynertCRHIL-1amygdalakindlingnucleus basalis of Meynert