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Nature. 2014 Dec 4;516(7529):51-5. doi: 10.1038/nature13976. Epub 2014 Nov 12.

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

Author information

1
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
2
Department of Psychiatry, University of Texas Southwestern, Dallas, Texas 75390, USA.
3
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

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.

PMID:
25383518
PMCID:
PMC4257892
DOI:
10.1038/nature13976
[Indexed for MEDLINE]
Free PMC Article

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