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Nat Commun. 2018 Mar 16;9(1):1116. doi: 10.1038/s41467-018-03567-4.

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

Author information

1
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA.
2
Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
3
School of Neuroscience, Virginia Polytechnic Institute and State University, 1981 Kraft Drive, Blacksburg, VA, 24061, USA.
4
Department of Neuroscience and Psychiatry, Faculty of Medicine, Laval University, 2601 Chemin de la Canardière Québec, QC, G1J 2G3, Canada.
5
Ludmer Centre for Neuroinformatics and Mental Health, Douglas Institute, Sackler Program for Epigenetics and Psychobiology, Departments of Psychiatry and Neurology and Neurosurgery, McGill University, 6875 Boulevard Lasalle, Montréal, QC, H4H 1R3, Canada.
6
Departments of Psychology & Psychiatry, Ludmer Centre for Neuroinformatics and Mental Health, McGill University, 1205 Avenue Dr Penfield, Montréal, QC, H3A 1B1, Canada.
7
Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY, 10029, USA. Eric.Nestler@mssm.edu.

Abstract

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.

PMID:
29549264
PMCID:
PMC5856766
DOI:
10.1038/s41467-018-03567-4
[Indexed for MEDLINE]
Free PMC Article

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