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磷酸化蛋白质组学分析揭示了睡眠剥夺对小鼠海马体的影响。

Phosphoproteomic analysis reveals the effects of sleep deprivation on the hippocampus in mice.

机构信息

School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, 230032, China.

State Key Laboratory of Proteomics, National Center for Protein Sciences-Beijing, Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, 102206, China.

出版信息

Mol Omics. 2022 Aug 15;18(7):677-685. doi: 10.1039/d2mo00061j.

Abstract

Sleep is essential for brain physiology, including nerve repair, neuronal activity, and metabolite clearance. The hippocampus is responsible for short-term memory, long-term memory, and spatial positioning. Herein, we investigated the effects of sleep deprivation on protein phosphorylation and related signaling pathways in the mouse hippocampus. The treatment group was sleep deprived for nine hours a day, and at the end of sleep deprivation, we removed the hippocampus for phosphoproteomic analysis. Through this analysis, we identified 65 sites and 27 proteins whose phosphorylation was significantly different between sleep-deprived animals and control animals. Differentially phosphorylated proteins (DPPs) were mainly distributed in the postsynaptic density, cytoplasm, and synapse. They participated in metabolic pathways, endocytosis, oxidative phosphorylation and other processes, and they were associated with Huntington's disease, Parkinson's disease, Alzheimer's disease, Functional analysis of the phosphoproteome shows that sleep deprivation significantly affects the level of protein phosphorylation in the hippocampus of mice. This is the first reported study that has used phosphoproteomics to investigate the effects of sleep deprivation on hypothalamic regions. This study provides data resources that can serve as a valuable reference for sleep mechanism research, sleep disorder treatment, and drug development.

摘要

睡眠对大脑生理学至关重要,包括神经修复、神经元活动和代谢物清除。海马体负责短期记忆、长期记忆和空间定位。在此,我们研究了睡眠剥夺对小鼠海马体蛋白磷酸化及相关信号通路的影响。实验组每天睡眠剥夺 9 小时,在睡眠剥夺结束时,我们取出海马体进行磷酸蛋白质组分析。通过这项分析,我们确定了 65 个位点和 27 种蛋白质,它们的磷酸化在睡眠剥夺动物和对照组动物之间有显著差异。差异磷酸化蛋白(DPP)主要分布在突触后密度、细胞质和突触中。它们参与代谢途径、内吞作用、氧化磷酸化等过程,与亨廷顿病、帕金森病、阿尔茨海默病有关。磷酸蛋白质组的功能分析表明,睡眠剥夺显著影响了小鼠海马体的蛋白磷酸化水平。这是首次使用磷酸蛋白质组学研究睡眠剥夺对下丘脑区域影响的报告。这项研究为睡眠机制研究、睡眠障碍治疗和药物开发提供了有价值的参考数据资源。

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