非快速眼动睡眠
神经科学
快速眼动睡眠
睡眠纺锤
黑质
睡眠(系统调用)
心理学
被盖腹侧区
多巴胺能
慢波睡眠
睡眠开始
眼球运动
多巴胺
脑电图
失眠症
精神科
计算机科学
操作系统
作者
Ying Chen,Wei-Ye Xie,Dong Xia,Mu-Tian Zhang,Yan-Rui Sun,Wen-Xiang Duan,Yun Shen,Fen Wang,Wei‐Min Qu,Zhi‐Li Huang,Chun‐Feng Liu
出处
期刊:npj Parkinson's disease
日期:2024-08-02
卷期号:10 (1)
标识
DOI:10.1038/s41531-024-00756-5
摘要
Abstract Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene ( GBA ) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA -AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.
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