The transcriptional regulator β-catenin has been implicated in neurological and psychiatric diseases, including depression. Eric Nestler and colleagues show that β-catenin in D2-type medium spiny neurons in the nucleus accumbens — an important brain reward region — mediates resilience to stress in mice. Transcriptional activity of β-catenin is reduced both in tissue taken post mortem from depressed humans and in mice that are susceptible to chronic stress. The authors also identify Dicer1 as a critical β-catenin target gene involved in mediating resilience, suggesting a novel regulatory mechanism for microRNA processing in the mature brain.
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