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Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus
Liao, Xue-Mei1,2; Yang, Xiao-Dun1,2; Jia, Jiao1,2,3; Li, Ji-Tao1,2; Xie, Xiao-Meng1,2; Su, Yun-Ai1,2; Schmidt, Mathias V.4; Si, Tian-Mei1,2; Wang, Xiao-Dong1,2,5
关键词Glucocorticoid Receptors Hippocampus Early-life Stress Synapse Corticotropin-releasing Hormone Receptor 1
刊名HIPPOCAMPUS
2014-05-01
DOI10.1002/hipo.22254
24期:5页:528-540
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]DENDRITIC SPINES ; GLUCOCORTICOID-RECEPTOR ; MATERNAL-CARE ; LONG-TERM ; PYRAMIDAL NEURONS ; DEXAMETHASONE TREATMENT ; ADHESION MOLECULE ; RAT HIPPOCAMPUS ; MEMORY FUNCTION ; IN-VIVO
英文摘要

Adult individuals with early stressful experience exhibit impaired hippocampal neuronal morphology, synaptic plasticity and cognitive performance. While our knowledge on the persistent effects of early-life stress on hippocampal structure and function and the underlying mechanisms has advanced over the recent years, the molecular basis of the immediate postnatal stress effects on hippocampal development remains to be investigated. Here, we reported that repeated blockade of corticotropin-releasing hormone receptor 1 (CRHR1) ameliorated postnatal stress-induced hippocampal synaptic abnormalities in neonatal mice. Following the stress exposure, pups with fragmented maternal care showed retarded dendritic outgrowth and spine formation in CA3 pyramidal neurons and reduced hippocampal levels of synapse-related proteins. During the stress exposure, repeated blockade of glucocorticoid receptors (GRs) by daily administration of RU486 (100 mu g g(-1)) failed to attenuate postnatal stress-evoked synaptic impairments. Conversely, daily administration of the CRHR1 antagonist antalarmin hydrochloride (20 mu g g(-1)) in stressed pups normalized hippocampal protein levels of synaptophysin, postsynaptic density-95, nectin-1, and nectin-3, but not the N-methyl-d-aspartate receptor subunits NR1 and NR2A. Additionally, GR or CRHR1 antagonism attenuated postnatal stress-induced endocrine alterations but not body growth retardation. Our data indicate that the CRH-CRHR1 system modulates the deleterious effects of early-life stress on dendritic development, spinogenesis, and synapse formation, and that early interventions of this system may prevent stress-induced hippocampal maldevelopment. (c) 2014 Wiley Periodicals, Inc.

语种英语
WOS记录号WOS:000333678200004
项目编号81171284 ; 30800361 ; 81301152 ; 20120001110046
资助机构National Natural Science Foundation of China ; Research Fund for the Doctoral Program of Higher Education of China ; International Brain Research Organization
引用统计
被引频次:29[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50239
专题北京大学精神卫生研究所
北京大学精神卫生研究所_精神科
北京大学精神卫生研究所_药理室
作者单位1.Peking Univ, Inst Mental Hlth, Beijing 100191, Peoples R China
2.Peking Univ, Key Lab Mental Hlth, Minist Hlth, Beijing 100191, Peoples R China
3.Shanxi Med Univ, Dayi Hosp, Dept Mental Hlth, Taiyuan 030032, Peoples R China
4.Max Planck Inst Psychiat, RG Neurobiol Stress, D-80804 Munich, Germany
5.Zhejiang Univ, Zhejiang Prov Key Lab Neurobiol, Key Lab Med Neurobiol, Dept Neurobiol,Minist Hlth China,Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714
Liao, Xue-Mei,Yang, Xiao-Dun,Jia, Jiao,et al. Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus[J]. HIPPOCAMPUS,2014,24(5):528-540.
APA Liao, Xue-Mei.,Yang, Xiao-Dun.,Jia, Jiao.,Li, Ji-Tao.,Xie, Xiao-Meng.,...&Wang, Xiao-Dong.(2014).Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus.HIPPOCAMPUS,24(5),528-540.
MLA Liao, Xue-Mei,et al."Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus".HIPPOCAMPUS 24.5(2014):528-540.
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