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

Author

Listed:
  • Zachary S. Lorsch

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Yong-Hwee Eddie Loh

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Immanuel Purushothaman

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Deena M. Walker

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Eric M. Parise

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Marine Salery

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Michael E. Cahill

    (University of Wisconsin-Madison)

  • Georgia E. Hodes

    (Virginia Polytechnic Institute and State University)

  • Madeline L. Pfau

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Hope Kronman

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Peter J. Hamilton

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Orna Issler

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Benoit Labonté

    (Laval University)

  • Ann E. Symonds

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Matthew Zucker

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Tie Yuan Zhang

    (McGill University)

  • Michael J. Meaney

    (McGill University)

  • Scott J. Russo

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Li Shen

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Rosemary C. Bagot

    (McGill University)

  • Eric J. Nestler

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

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.

Suggested Citation

  • Zachary S. Lorsch & Yong-Hwee Eddie Loh & Immanuel Purushothaman & Deena M. Walker & Eric M. Parise & Marine Salery & Michael E. Cahill & Georgia E. Hodes & Madeline L. Pfau & Hope Kronman & Peter J. , 2018. "Estrogen receptor α drives pro-resilient transcription in mouse models of depression," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03567-4
    DOI: 10.1038/s41467-018-03567-4
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