beta-catenin mediates stress resilience through Dicer1/microRNA regulation

Article

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

DOI  :  10.1038/nature13976

来源: SCIE

【 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.

【 授权许可】

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