Most people exposed to stress do not develop depression. Animal models have shown that stress resilience is an active state that requires broad transcriptional adaptations, but how this homeostatic process is regulated remains poorly understood. In this study, we analyze upstream regulators of genes differentially expressed after chronic social defeat stress. We identify estrogen receptor  (ER) as the top regulator of pro-resilient transcriptional changes in the nucleus accumbens (NAc), a key brain reward region implicated in depression. In accordance with these findings, nuclear ER protein levels are altered by stress in male and female mice. Further, overexpression of ER in the NAc promotes stress resilience in both sexes. Subsequent RNA sequencing reveals that ER overexpression in NAc reproduces the transcriptional signature of resilience in male, but not female, mice. These results indicate that NAc ER is an important regulator of pro-resilient transcriptional changes, but with sex-specific downstream targets. SOURCE: Aarthi Ramakrishnan (aarthi.ramakrishnan@mssm.edu) -  Icahn School of Medicine at Mount Sinai

Pluto Bioinformatics

GSE110725: Estrogen Receptor Drives Pro-Resilient Transcription in Mouse Models of Depression