The Nucleus Accumbens CRH–CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse
作者机构：Peking University Sixth HospitalPeking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing100191China Department of PharmacologySchool of Basic Medical SciencesState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceFudan UniversityShanghai200032China
出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)
年 卷 期：2023年第39卷第1期
页 面：41-56页
核心收录：
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100205[医学-精神病与精神卫生学] 10[医学]
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)
主 题：Early-life stress Sleep CRH-CRHR1 Nucleus accumbens Morphology
摘 要：Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood,one of which is sleep *** 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 *** 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 *** 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 ***,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.
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