β-catenin mediates stress resilience through Dicer1/microRNA regulation.

Titleβ-catenin mediates stress resilience through Dicer1/microRNA regulation.
Publication TypeJournal Article
Year of Publication2014
AuteursDias, C, Feng, J, Sun, H, Shao, NYi, Mazei-Robison, MS, Damez-Werno, D, Scobie, K, Bagot, R, Labonté, B, Ribeiro, E, Liu, XC, Kennedy, P, Vialou, V, Ferguson, D, Peña, C, Calipari, ES, Koo, JWook, Mouzon, E, Ghose, S, Tamminga, C, Neve, R, Shen, L, Nestler, EJ
JournalNature
Volume516
Pagination51-5
Date Published2014 Dec 04
ISSN1476-4687
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.

DOI10.1038/nature13976