自闭症儿童睡眠障碍神经机制研究进展

Research progress on the neural mechanisms of sleep disorders in autistic children

睡眠障碍在自闭症谱系障碍(autismspectrumdisorder,ASD)儿童中发病率很高。睡眠障碍会加剧ASD儿童病程发展,增加护理难度和成本,给家庭和社会造成沉重负担,因此具有重要研究价值。对导致ASD儿童睡眠障碍的神经机制的研究表明,睡眠-觉醒相关神经环路结构功能异常与睡眠障碍发生发展密切相关。首先,ASD儿童蓝斑(locuscoeruleus,LC)-去甲肾上腺素(noradrenaline,NE)系统超兴奋活动、下丘脑后部组胺受体增加、下丘脑外侧-食欲素系统活动增强以及中脑黑质致密部多巴胺转运体功能异常可导致其觉醒延长。其次,ASD儿童丘脑网状核功能异常,短链脂肪酸、铁元素、维生素A等物质水平降低会导致其非快速眼动(non-rapid eye movement,NREM)睡眠异常,而中缝背核5-羟色胺能神经元活动增强以及杏仁核调控作用异常可扰乱其快速眼动(rapid eye movement, REM)睡眠。此外,ASD儿童脑内褪黑素水平降低和基底前脑胆碱能神经元结构功能改变可导致其睡眠时相转换异常。因此,研究ASD儿童睡眠障碍病理特征并探索其神经机制对进一步寻找针对其核心症状的治疗新策略具有重要意义。

The incidence of sleep disorder is very high in children with autism spectrum disorder(ASD).Sleep disorders can aggravate the development of ASD,increase the difficulty and cost of care,and cause heavy burden to family and society,and therefore have important research value.According to the study of the neural mechanism leading to sleep disorders in children with ASD,the functional and structural abnormalities of sleep-wakefulness related neural circuits are strongly correlated with the occurrence and development of sleep disorders.Firstly,hyperexcitability of the locus coeruleus-norepinephrine system,increased histamine receptors expression in the posterior hypothalamus,hyperexcitability of the lateral hypothalamus-orexin system and dysfunction of the dopamine transporters in the substantia nigra pars compacta may lead to extended arousal of ASD children.Secondly,dysfunction of thalamic reticular nucleus,reduced levels of short-chain fatty acids,ion,vitamin A and other substances may induce non-rapid eye movement(NREM) sleep disorders,while the increased activity of serotonergic neurons in the dorsal raphe nucleus and the abnormal regulatory effects of the amygdala in ASD children may disturb rapid eye movement(REM) sleep.In addition,decreased levels of melatonin and functional alterations of basal forebrain cholinergic neurons in ASD children may lead to abnormal sleep-wakefulness rhythm transitions.It is of great significance to study the pathological features and the underlying neural mechanism of sleep disorders in ASD children for finding new treatment strategies for their core symptoms.