Estrogen receptor α drives pro-resilient transcription in mouse models of depression.

TitleEstrogen receptor α drives pro-resilient transcription in mouse models of depression.
Publication TypeJournal Article
Year of Publication2018
AuthorsLorsch ZS, Loh Y-HEddie, Purushothaman I, Walker DM, Parise EM, Salery M, Cahill ME, Hodes GE, Pfau ML, Kronman H, Hamilton PJ, Issler O, Labonte B, Symonds AE, Zucker M, Zhang TYuan, Meaney MJ, Russo SJ, Shen L, Bagot RC, Nestler EJ
JournalNat Commun
Date Published2018 Mar 16

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 α (ERα) 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 ERα protein levels are altered by stress in male and female mice. Further, overexpression of ERα in the NAc promotes stress resilience in both sexes. Subsequent RNA-sequencing reveals that ERα overexpression in NAc reproduces the transcriptional signature of resilience in male, but not female, mice. These results indicate that NAc ERα is an important regulator of pro-resilient transcriptional changes, but with sex-specific downstream targets.

Alternate JournalNat Commun
PubMed ID29549264
PubMed Central IDPMC5856766