Sleep Deprivation Selectively Down-Regulates Astrocytic 5-HT2B Receptors and Triggers Depressive-Like Behaviors via Stimulating P2X7 Receptors in Mice  

作　　者：Maosheng Xia Zexiong Li Shuai Li Shanshan Liang Xiaowei Li Beina Chen Manman Zhang Chengyi Dong Alexei Verkhratsky Dawei Guan Baoman Li 

机构地区：[1]Practical Teaching Centre,School of Forensic Medicine,China Medical University,Shenyang 110122,China [2]Department of Orthopaedics,The First Hospital,China Medical University,Shenyang 110001,China [3]Faculty of Biology,Medicine and Health,The University of Manchester,Manchester M139PL,UK [4]Department of Forensic Pathology,School of Forensic Medicine,China Medical University,Shenyang 110122,China [5]Department of Poison Analysis,School of Forensic Medicine,China Medical University,Shenyang 110122,China

出　　处：《Neuroscience Bulletin》2020年第11期1259-1270,共12页神经科学通报（英文版）

基　　金：the National Natural Science Foundation of China(81871852,81200935,81671862,and 81871529);Liaoning Revitalization Talents Program(XLYC1807137);the Scientific Research Foundation for Overseas Scholars of the Education Ministry of China(20151098);the Natural Science Foundation of Liaoning Province,China(20170541030)。

摘　　要：Chronic loss of sleep damages health and disturbs the quality of life.Long-lasting sleep deprivation(SD)as well as sleep abnormalities are substantial risk factors for major depressive disorder,although the underlying mechanisms are not clear.Here,we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP,which activates astroglial P2X7 receptors(P2X7Rs).Activated P2X7Rs,in turn,selectively down-regulated the expression of 5-HT2B receptors(5-HT2BRs)in astrocytes.Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3 a in astrocytes,but not in neurons.The overexpression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs.Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2.This latter cascade promoted the release of arachidonic acid and prostaglandin E2.The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice.Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders.

关 键 词：ASTROCYTE Sleep deprivation P2X7 receptor 5-HT2B receptor FOXO3A 

分 类 号：R74[医药卫生—神经病学与精神病学]