β-catenin mediates stress resilience through Dicer1/microRNA regulation

被引：202

作者：

Dias, Caroline ^{[1
,2
]}

Feng, Jian ^{[1
,2
]}

Sun, Haosheng ^{[1
,2
]}

Shao, Ning yi ^{[1
,2
]}

Mazei-Robison, Michelle S. ^{[1
,2
]}

Damez-Werno, Diane ^{[1
,2
]}

Scobie, Kimberly ^{[1
,2
]}

Bagot, Rosemary ^{[1
,2
]}

LaBonte, Benoit ^{[1
,2
]}

Ribeiro, Efrain ^{[1
,2
]}

Liu, XiaoChuan ^{[1
,2
]}

Kennedy, Pamela ^{[1
,2
]}

Vialou, Vincent ^{[1
,2
]}

Ferguson, Deveroux ^{[1
,2
]}

Pena, Catherine ^{[1
,2
]}

Calipari, Erin S. ^{[1
,2
]}

Koo, Ja Wook ^{[1
,2
]}

Mouzon, Ezekiell ^{[1
,2
]}

Ghose, Subroto ^{[3
]}

Tamminga, Carol ^{[3
]}

Neve, Rachael ^{[4
]}

Shen, Li ^{[1
,2
]}

Nestler, Eric J. ^{[1
,2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[3] Univ Texas Southwestern, Dept Psychiat, Dallas, TX 75390 USA

[4] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA

来源：

NATURE | 2014年 / 516卷 / 7529期

关键词：

NUCLEUS-ACCUMBENS; DISTINCT ROLES; SOCIAL DEFEAT; SYNTHASE KINASE-3; STRIATAL NEURONS; TRANSCRIPTION; PATHWAY; REWARD; BDNF; IDENTIFICATION;

D O I：

10.1038/nature13976

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

beta-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice beta-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide beta-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis-as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin fromnucleus accumbens in the context of chronic stress reveals beta-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish beta-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. Wethus present a foundation for the development of novel therapeutic targets to promote stress resilience.

引用

页码：51 / U86

页数：17

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