수면-각성 조절의 신경해부학과 그의 약물 치료적 적용 = Neuroanatomy of Sleep-Wake Regulation and its Application to Pharmacotherapy

다국어 초록 (Multilingual Abstract)

A current hypothesis of sleep–wake regulation proposes that the sleep process starts with the activation of sleep-promoting neurons located in the preoptic area of the anterior hypothalamus. This activation leads to the inhibition of wake-promoting neurons located in the posterior hypothalamus, basal forebrain, and mesopontine tegmentum, which in turn removes inhibition from the sleep-promoting structures (i.e., disinhibition) to initiatethe sleep process. Mutual inhibition between these wake- and sleep-promoting neurons results in switching properties that define discrete wakeful and sleep states with sharp transitions between them. Wake-promoting nuclei include the orexinergic lateral hypothalamic/perifornical area, the histaminergic tuberomammillary nucleus, the cholinergic pedunculopontine tegmental nucleus, the noradrenergic locus coeruleus, the 5-hydroxytryptaminergic raphe nuclei, and possibly the dopaminergic ventral tegmental area.The major sleep-promoting nucleus is the GABAergic ventrolateral preoptic nucleus of the hypothalamus. The regulation of sleep is classically viewed as the dual interaction of circadian (SCN-based) and homeostatic processes, and the propensity to be asleep or awake at any given time is a consequence of a sleep debt and its interaction with signals from the SCN circadian clock. To better understand the mechanisms of sleep and wakefulness, the focus of pharmacotherapy is on targeting specific therapies to the particular defect in sleep–wake regulation.

국문 초록 (Abstract)

수면-각성 조절에 대한 현재의 이론은 수면 과정이 전시상하부의 시각전영역에 위치한 수면-촉진 뉴런의 활성과 함께 시작된다는 것을 제시한다. 이러한 활성은 후시상하부, 전뇌기저부, 그리고 중간교뇌피개에 위치한 각성-촉진 뉴런의 억제를 초래하고 이것이 연이어 수면-촉진 부위로부터의 억제를 무력화(즉, 탈억제)시켜 수면 과정을 증가시킨다. 각성 및 수면-촉진 뉴런 사이의 상호 억제 작용을 통해서 각성 상태와 수면 상태 사이에 신속한 전환이 이루어지게 하여 이들 각각은 불연속적인 상태를 유지하게 하는 스위치의 특성을 지니게 한다. 각성-촉진 뉴런 집합체는 orexin을 함유하고 있는 외측시상하부/뇌궁주위 영역, 히스타민성 조면유도체핵, 콜린성 중간교뇌피개, 노르아드레날린성 청반핵, 세로토닌성 솔기핵, 그리고 도파민성 배쪽피개영역 등을 포함한다. 주요 수면-촉진 뉴런 집합체는 시상하부의 GABA성 배쪽외측시각전핵이다. 수면의 조절은 전형적으로 일주기 조절 과정(시신경교차상핵과 관련됨)과 항상성 조절 과정의 상호작용으로 일어난다는 관점을 견지하고 있다. 어떤 주어진 시기에 각성 혹은 수면을 취할지에 대한 성향은 수면 부담(혹은 욕구)의 정도와 시신경교차상핵의 일주기 시계로부터 전해지는 신호의 상호작용에 의해 결정된다. 수면과 각성에 대한 이러한 기전을 더욱 잘 이해함으로서 향후에는 수면-각성 조절에 관여하는 뇌의 여러 영역들 중에서 결함이 있는 특정 부위에 대해 좀 더 특이적인 약물 치료적 개입이 가능할 것이다.

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