We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
β-catenin mediates stress resilience through Dicer1/microRNA regulation.
- Authors
Dias, Caroline; Feng, Jian; Sun, Haosheng; Shao, Ning yi; Mazei-Robison, Michelle S.; Damez-Werno, Diane; Scobie, Kimberly; Bagot, Rosemary; LaBonté, Benoit; Ribeiro, Efrain; Liu, XiaoChuan; Kennedy, Pamela; Vialou, Vincent; Ferguson, Deveroux; Peña, Catherine; Calipari, Erin S.; Koo, Ja Wook; Mouzon, Ezekiell; Shen, Li; Nestler, Eric J.
- Abstract
β-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 β-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 β-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis-as a β-catenin target gene that mediates resilience. Small RNA profiling after excising β-catenin from nucleus accumbens in the context of chronic stress reveals β-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish β-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.
- Subjects
CATENINS; PSYCHOLOGICAL stress; MICRORNA; MENTAL depression; CENTRAL nervous system; HUMAN genome
- Publication
Nature, 2014, Vol 516, Issue 7529, p51
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature13976