Study on a neuronal population essential for REM sleep and its involvement in Parkinson's disease

快速眼动睡眠必需的神经元群及其与帕金森病的关系研究

• 批准号: 21K15617
• 负责人: Liu ChihーYao
• 金额: $ 3万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K15617/
• 关键词: Sleep; REM sleep; Sublaterodorsal nucleus; Parkinson's disease; Alpha-synuclein; alpha-synuclein

Mammalian sleep is composed of rapid eye movement (REM) sleep and non-REM (NREM) sleep, both of which can be compromised differentially in various psychiatric and neurological disorders. I recently found that ablation of a specific neuronal population in the sublaterodorsal nucleus (SLD) resulted in significant loss of REM sleep, suggesting a genetically defined neuronal population is discovered to be essential for generating REM sleep. In the SLD neuron-ablated mice, REM sleep without muscle atonia is frequently observed, reminiscent of REM sleep behavior disorder in Parkinson's disease (PD). Moreover, lower anxiety-like and lower depression-like behaviors are found, consistent with previous observations in which REM sleep deprivation produced anxiolytic-like and antidepressant-like effect. Next, I found that the ablated neuronal population are composed of both GABAergic and glutamatergic neurons with varied percentages. Therefore, these results provide us more information about the pathogenesis of PD, during which the alpha-synuclein accumulation may occur in the level of the SLD, producing various motor and non-motor symptoms. Furthermore, the genetic identification of SLD neurons may lead to the development of novel diagnostic methods and therapeutics for PD.

哺乳动物的睡眠由快速眼动（REM）睡眠和非REM（NREM）睡眠组成，这两种睡眠在各种精神和神经疾病中可能受到不同的损害。我最近发现，在sublaterodorporal核（SLD）的特定神经元群体的消融导致REM睡眠的显着损失，这表明基因定义的神经元群体被发现是产生REM睡眠必不可少的。在SLD神经元消融的小鼠中，经常观察到没有肌肉张力的REM睡眠，这让人想起帕金森病（PD）中的REM睡眠行为障碍。此外，较低的焦虑和抑郁样行为被发现，与以前的观察，其中快速眼动睡眠剥夺产生抗焦虑和抗抑郁样的效果。接下来，我发现消融的神经元群体由不同百分比的GABA能和谷氨酸能神经元组成。因此，这些结果为我们提供了更多关于PD发病机制的信息，在此期间，α-突触核蛋白积聚可能发生在SLD水平，产生各种运动和非运动症状。此外，SLD神经元的遗传鉴定可能会导致PD新的诊断方法和治疗方法的发展。