title: Early postnatal stress suppresses the developmental trajectory of hippocampal pyramidal neurons: the role of CRHR1.
abstract: Adverse experiences early in life hamper the development and maturation of the hippocampus, but how early-life stress perturbs the developmental trajectory of the hippocampus across various life stages and the underlying molecular mechanisms remain to be investigated. In this study, we stressed male mice from postnatal day 2 (P2) to P9, and examined the potential role of CRHR1 in postnatal stress-induced structural remodeling of hippocampal CA3 pyramidal neurons directly after stress (P9), in mid-adolescence (P35) and in adulthood (P90). We found that early-life stress exposure significantly reduced apical dendritic arborization and spine density in CA3 neurons on P9 and P90. Moreover, postnatally stressed neurons underwent increased pruning of spines, especially thin spines, between P35 and P90. These stress-induced immediate and long-term structural abnormalities could be abolished by daily systemic administration of the CRHR1 antagonist antalarmin (20 µg/g of body weight) during stress exposure. However, such treatment strategy failed to attenuate the deleterious stress effects in mid-adolescence on P35. We then extended antalarmin treatment until the end of the second postnatal week, and found that prolonged blockade of CRHR1 could prevent the mid-term impact of early postnatal stress on structural remodeling of CA3 neurons. Our study characterized the influences of early-life stress on the developmental trajectory of hippocampal pyramidal neurons, and highlighted the critical role of CRHR1 in modulating these negative outcomes evoked by early-life stress.
authors.affiliation: Peking University Sixth Hospital (Institute of Mental Health), Beijing, 100191, China.|National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Peking University Sixth Hospital (Institute of Mental Health), Beijing, 100191, China.|National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
authors.forename: Xiao-Dun
authors.initials: XD
authors.lastname: Yang
authors.affiliation: Peking University Sixth Hospital (Institute of Mental Health), Beijing, 100191, China.|National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Liao
authors.affiliation: Peking University Sixth Hospital (Institute of Mental Health), Beijing, 100191, China.|National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Xie
authors.affiliation: Peking University Sixth Hospital (Institute of Mental Health), Beijing, 100191, China.|National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
authors.forename: Yun-Ai
authors.initials: YA
authors.lastname: Su
authors.affiliation: Peking University Sixth Hospital (Institute of Mental Health), Beijing, 100191, China.|National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China.
authors.forename: Ji-Tao
authors.initials: JT
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China. dr.xiaodong.wang@gmail.com.
authors.forename: Xiao-Dong
authors.identifier: 0000-0001-7730-3710
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Peking University Sixth Hospital (Institute of Mental Health), Beijing, 100191, China. si.tian-mei@163.com.|National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, 100191, China. si.tian-mei@163.com.
authors.forename: Tian-Mei
authors.initials: TM
authors.lastname: Si
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000254:growth & development* / Q000473:pathology; D049229:Dendritic Spines / Q000473:pathology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology*; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*; D000099052:CRF Receptor, Type 1
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000099052:CRF Receptor, Type 1
keywords: Corticotropin-releasing hormone receptor 1; Dendrite; Early-life stress; Hippocampus; Spine