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学科主题: 精神卫生
题名:
Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus
作者: 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
发表日期: 2014-05-01
DOI: 10.1002/hipo.22254
卷: 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
所属项目编号: 81171284 ; 30800361 ; 81301152 ; 20120001110046
项目资助者: National Natural Science Foundation of China ; Research Fund for the Doctoral Program of Higher Education of China ; International Brain Research Organization
WOS记录号: WOS:000333678200004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50239
Appears in Collections:北京大学精神卫生研究所_期刊论文

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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

Recommended Citation:
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.
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