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DOI | 10.1126/science.aan4491 |
Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2 | |
Pena, Catherine J.1; Kronman, Hope G.1; Walker, Deena M.1; Cates, Hannah M.1; Bagot, Rosemary C.1,4; Purushothaman, Immanuel1; Issler, Orna1; Loh, Yong-Hwee Eddie1; Leong, Tin1; Kiraly, Drew D.1,2; Goodman, Emma1; Neve, Rachael L.3; Shen, Li1; Nestler, Eric J.1 | |
2017-06-16 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 356期号:6343页码:1185-1188 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Canada |
英文摘要 | Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like state. We identify a role for the developmental transcription factor orthodenticle homeobox 2 (Otx2) as an upstream mediator of these enduring effects. Transient juvenile-but not adult-knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, whereas its overexpression reverses the effects of early life stress. This work establishes a mechanism by which early life stress encodes lifelong susceptibility to stress via long-lasting transcriptional programming in VTA mediated by Otx2. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000403327400041 |
WOS关键词 | MAJOR DEPRESSION ; CHILDHOOD ; RESPONSES ; DOPAMINE ; TRAUMA |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/196263 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Icahn Sch Med Mt Sinai, Friedman Brain Inst, Fishberg Dept Neurosci, New York, NY 10029 USA; 2.Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Psychiat, New York, NY 10029 USA; 3.MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA; 4.McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada |
推荐引用方式 GB/T 7714 | Pena, Catherine J.,Kronman, Hope G.,Walker, Deena M.,et al. Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2[J]. SCIENCE,2017,356(6343):1185-1188. |
APA | Pena, Catherine J..,Kronman, Hope G..,Walker, Deena M..,Cates, Hannah M..,Bagot, Rosemary C..,...&Nestler, Eric J..(2017).Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2.SCIENCE,356(6343),1185-1188. |
MLA | Pena, Catherine J.,et al."Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2".SCIENCE 356.6343(2017):1185-1188. |
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