The Nucleus Accumbens CRH–CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse  

作　　者：Ting Wang Yu-Nu Ma Chen-Chen Zhang Xiao Liu Ya-Xin Sun Hong-Li Wang Han Wang Yu-Heng Zhong Yun-Ai Su Ji-Tao Li Tian-Mei Si 

机构地区：[1]Peking University Sixth Hospital,Peking University Institute of Mental Health,NHC Key Laboratory of Mental Health(Peking University),National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital),Beijing,100191,China [2]Department of Pharmacology,School of Basic Medical Sciences,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai,200032,China

出　　处：《Neuroscience Bulletin》2023年第1期41-56,共16页神经科学通报（英文版）

基　　金：supported by the National Key Basic Research Program of China(973 Program,2015CB856401);the Beijing National Science Foundation(7222236);the Capital Medical Development Research Fund(2020-2-4113);the National Natural Science Foundation of China(81630031,81771468,82071528,and 82171529).

摘　　要：Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood,one of which is sleep disturbance.As the corticotropin-releasing hormone(CRH)–corticotropin-releasing hormone receptor 1(CRHR1)system and nucleus accumbens(NAc)play important roles in both stress responses and sleep-wake regulation,in this study we investigated whether the NAc CRH–CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice.Using the limited nesting and bedding material paradigm from postnatal days 2 to 9,we found that early-life stress disrupted sleep-wake behaviors during adulthood,including increased wakefulness and decreased non-rapid eye movement(NREM)sleep time during the dark period and increased rapid eye movement(REM)sleep time during the light period.The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure.Importantly,Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology,whereas NAc Crhr1 knockdown reversed these effects(including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy).Together,our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc,and highlight the critical role of the NAc CRH–CRHR1 system in modulating these negative outcomes evoked by early-life stress.

关 键 词：Early-life stress SLEEP CRH-CRHR1 Nucleus accumbens MORPHOLOGY 

分 类 号：R749.71[医药卫生—神经病学与精神病学]