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】
Free