Department of Neurology and F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, United States.
Department of Neurology and F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, United States; Division of Sleep Medicine, Harvard Medical School, United States.
Neurobiol Learn Mem. 2019 Apr;160:160-172. doi: 10.1016/j.nlm.2019.01.011. Epub 2019 Jan 19.
Sleep is a mysterious, developmentally regulated behavior fundamental for cognition in both adults and developing animals. A large number of studies offer a substantive body of evidence that demonstrates that the ontogeny of sleep architecture parallels brain development. Sleep deprivation impairs the consolidation of learned tasks into long-term memories and likely links sleep to the neural mechanisms underlying memory and its physiological roots in brain plasticity. Consistent with this notion is the alarming frequency of sleep and circadian rhythm dysfunction in children with neurodevelopmental disorders (NDDs). While the mechanisms underlying sleep dysfunction in most NDDs still remains poorly understood, here we will review several sentinel examples of monogenetic NDDs with both well-established connections to synaptic dysfunction and evidence of sleep or circadian dysfunction: Tuberous Sclerosis Complex, Fragile X Syndrome, and Angelman Syndrome. We suggest that the coincident maturation of sleep with synaptic physiology is one of the core reasons for the commonplace disruption of sleep in NDDs and argue that disorders with well-defined molecular genetics can provide a unique lens for understanding and unraveling the molecular correlates that link the development of sleep and circadian rhythms to health and disease.
睡眠是一种神秘的、发育调节的行为，对成年人和发育中的动物的认知都至关重要。大量研究提供了大量证据，表明睡眠结构的发生与大脑发育相平行。睡眠剥夺会损害已学习任务向长期记忆的巩固，并可能将睡眠与记忆的神经机制及其在大脑可塑性中的生理基础联系起来。这一观点与神经发育障碍（NDD）儿童中睡眠和昼夜节律功能障碍的惊人频率是一致的。虽然大多数 NDD 中睡眠功能障碍的机制仍知之甚少，但在这里，我们将回顾几种单基因 NDD 的典型例子，这些疾病都与突触功能障碍有明确的联系，并具有睡眠或昼夜节律功能障碍的证据：结节性硬化症、脆性 X 综合征和 Angelman 综合征。我们认为，睡眠与突触生理学的同时成熟是 NDD 中睡眠普遍中断的核心原因之一，并认为具有明确分子遗传学的疾病可以为理解和揭示将睡眠和昼夜节律的发育与健康和疾病联系起来的分子相关性提供独特的视角。
