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学科主题: 精神卫生
题名:
Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior
作者: Li, Jun1,2,3; Chai, Anping4,5,6; Wang, Lifang1,2,3; Ma, Yuanlin1,2,3; Wu, Zhiliu1,2,3; Yu, Hao1,2,3; Mei, Liwei1,2,3; Lu, Lin1,2,3; Zhang, Chen8; Yue, Weihua1,2,3; Xu, Lin4,5,6; Rao, Yi7,8,9; Zhang, Dai1,2,3,8,9,10
关键词: autism ; social recognition ; P-Rex1 ; long-term depression ; AMPA receptor endocytosis
刊名: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
发表日期: 2015-12-15
DOI: 10.1073/pnas.1512913112
卷: 112, 期:50, 页:E6964-E6972
收录类别: SCI ; SSCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: AMPA RECEPTOR ENDOCYTOSIS ; NUCLEOTIDE-EXCHANGE FACTOR ; MORRIS WATER MAZE ; MICE LACKING ; MEMORY ; PROTEIN ; FLEXIBILITY ; LTD ; RAC ; ACTIVATION
英文摘要:

Autism spectrum disorders (ASDs) are a group of highly inheritable mental disorders associated with synaptic dysfunction, but the underlying cellular and molecular mechanisms remain to be clarified. Here we report that autism in Chinese Han population is associated with genetic variations and copy number deletion of P-Rex1 (phosphatidylinosito1-3,4,5-trisphosphate-dependent Rac exchange factor 1). Genetic deletion or knockdown of P-Rex1 in the CM region of the hippocampus in mice resulted in autism-like social behavior that was specifically linked to the defect of long-term depression (LTD) in the CM region through alteration of AMPA receptor endocytosis mediated by the postsynaptic PP1 alpha (protein phosphase 1 alpha)-P-Rex1-Rac1 (Ras-related C3 botulinum toxin substrate 1) signaling pathway. Rescue of the LTD in the CM region markedly alleviated autism-like social behavior. Together, our findings suggest a vital role of P-Rex1 signaling in CM LTD that is critical for social behavior and cognitive function and offer new insight into the etiology of ASDs.

语种: 英语
所属项目编号: 2010CB833905 ; 2013CB835103 ; 91232305 ; 81471360 ; 81222017 ; 81471383 ; 81221002 ; 81501183 ; JC201104220331A
项目资助者: Program 973 of the Ministry of Science and Technology of China ; National Natural Science Foundation of China ; Shenzhen Basic Research Grant
WOS记录号: WOS:000366404200019
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53313
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, Sch Life Sci, Beijing 100871, Peoples R China
2.Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China
3.Peking Univ, Minist Hlth, Natl Clin Res Ctr Mental Disorders, Beijing 100191, Peoples R China
4.Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100191, Peoples R China
5.Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China
6.Chinese Acad Sci, Kunming Inst Zool, Chinese Univ Hong Kong Joint Lab Bioresources & M, Kunming 650223, Yunnan, Peoples R China
7.Chinese Acad Sci, Kunming Inst Zool, Lab Learning & Memory, Kunming 650223, Yunnan, Peoples R China
8.Peking Univ, Int Data Grp, McGovern Inst Brain Res, Beijing 100871, Peoples R China
9.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
10.Shenzhen Peking Univ, Univ Hong Kong Univ Sci & Technol, Shenzhen Key Lab Neuronal Struct Biol, Med Ctr, Shenzhen 518035, Peoples R China

Recommended Citation:
Li, Jun,Chai, Anping,Wang, Lifang,et al. Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(50):E6964-E6972.
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