首页|The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse
The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse
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Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adult-hood,one of which is sleep disturbance.As the cortico-tropin-releasing hormone(CRH)-corticotropin-releasing hormone receptor 1(CRHR1)system and nucleus accum-bens(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 para-digm 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 dur-ing 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.
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
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
National Key Basic Research Program of ChinaNational Key Basic Research Program of ChinaBeijing National Science FoundationCapital Medical Development Research FundNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China
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