■自闭症谱系障碍（ASD）儿童的睡眠障碍发生率很高。睡眠障碍会加剧ASD的发展，给家庭和社会带来沉重负担。自闭症患者睡眠障碍的病理机制复杂,但可能涉及基因突变和神经异常。
■在这篇评论中，我们研究了有关ASD儿童睡眠障碍的遗传和神经机制的文献。在PubMed和Scopus数据库中搜索了2013年至2023年之间发表的合格研究。
■ASD儿童的长时间觉醒可能是由以下过程引起的。MECP2，VGAT和SLC6A1基因的突变可以降低GABA对蓝斑神经元的抑制作用，导致ASD儿童的去甲肾上腺素能神经元过度活跃和长时间的觉醒。HRH1，HRH2和HRH3基因的突变会增强下丘脑后部组胺受体的表达，可能增强组胺促进唤醒的能力。KCNQ3和PCDH10基因的突变导致杏仁核对食欲能神经元的影响的非典型调节，可能导致下丘脑食欲素系统的过度兴奋。AHI1,ARHGEF10,UBE3A,和SLC6A3基因影响多巴胺合成，分解代谢，和再摄取过程，可以提高中脑多巴胺的浓度.其次,非快速眼动睡眠障碍与丁酸缺乏密切相关，铁缺乏和PTCHD1基因改变引起的丘脑网状核功能障碍。第三，HTR2A中的突变，SLC6A4,MAOA,MAOB,TPH2,VMATs,SHANK3和CADPS2基因诱导背中缝核（DRN）和杏仁核的结构和功能异常，这可能会干扰REM睡眠。此外,ASMT引起的褪黑激素水平下降，MTNR1A,和MTNR1B基因突变，伴随着基底前脑胆碱能神经元的功能异常，可能导致异常的睡眠-觉醒节律转换。
■我们的综述显示，基因突变引起的睡眠-觉醒相关神经回路的功能和结构异常与ASD儿童的睡眠障碍密切相关。探索ASD儿童睡眠障碍的神经机制和潜在的遗传病理学对于进一步研究治疗具有重要意义。
UNASSIGNED: The incidence of sleep disorders in children with autism spectrum disorder (ASD) is very high. Sleep disorders can exacerbate the development of ASD and impose a heavy burden on families and society. The pathological mechanism of sleep disorders in autism is complex, but gene mutations and neural abnormalities may be involved.
UNASSIGNED: In this
review, we examined literature addressing the genetic and neural mechanisms of sleep disorders in children with ASD. The databases PubMed and Scopus were searched for eligible studies published between 2013 and 2023.
UNASSIGNED: Prolonged awakenings of children with ASD may be caused by the following processes. Mutations in the MECP2, VGAT and SLC6A1 genes can decrease GABA inhibition on neurons in the locus coeruleus, leading to hyperactivity of noradrenergic neurons and prolonged awakenings in children with ASD. Mutations in the HRH1, HRH2, and HRH3 genes heighten the expression of histamine receptors in the posterior hypothalamus, potentially intensifying histamine\'s ability to promote arousal. Mutations in the KCNQ3 and PCDH10 genes cause atypical modulation of amygdala impact on orexinergic neurons, potentially causing hyperexcitability of the hypothalamic orexin system. Mutations in the AHI1, ARHGEF10, UBE3A, and SLC6A3 genes affect dopamine synthesis, catabolism, and reuptake processes, which can elevate dopamine concentrations in the midbrain. Secondly, non-rapid eye movement sleep disorder is closely related to the lack of butyric acid, iron deficiency and dysfunction of the thalamic reticular nucleus induced by PTCHD1 gene alterations. Thirdly, mutations in the HTR2A, SLC6A4, MAOA, MAOB, TPH2, VMATs, SHANK3, and CADPS2 genes induce structural and functional abnormalities of the dorsal raphe nucleus (DRN) and amygdala, which may disturb REM sleep. In addition, the decrease in melatonin levels caused by ASMT, MTNR1A, and MTNR1B gene mutations, along with functional abnormalities of basal forebrain cholinergic neurons, may lead to abnormal sleep-wake rhythm transitions.
UNASSIGNED: Our
review revealed that the functional and structural abnormalities of sleep-wake related neural circuits induced by gene mutations are strongly correlated with sleep disorders in children with ASD. Exploring the neural mechanisms of sleep disorders and the underlying genetic pathology in children with ASD is significant for further studies of therapy.
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