Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behavior

Ja Wook Koo, Scott J. Russo, Deveroux Ferguson, Eric J. Nestler, Ronald S. Duman

Research output: Contribution to journalArticle

345 Scopus citations

Abstract

Proinflammatory cytokines, such as IL-1β, have been implicated in the cellular and behavioral effects of stress and in mood disorders, although the downstream signaling pathways underlying these effects have not been determined. In the present study, we demonstrate a critical role for NF-κB signaling in the actions of IL-1β and stress. Stress inhibition of neurogenesis in the adult hippocampus, which has been implicated in the prodepressive effects of stress, is blocked by administration of an inhibitor of NF-κB. Further analysis reveals that stress activates NF-κB signaling and decreases proliferation of neural stem-like cells but not early neural progenitor cells in the adult hippocampus.We also find that depressive-like behaviors caused by exposure to chronic stress are mediated by NF-κB signaling. Together, these data identify NF-κB signaling as a critical mediator of the antineurogenic and behavioral actions of stress and suggest previouslyundescribedtherapeutical targets for depression.

Original languageEnglish (US)
Pages (from-to)2669-2674
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number6
DOIs
StatePublished - Feb 9 2010
Externally publishedYes

Keywords

  • Cytokine
  • Depression
  • IL-1
  • Inflammation
  • Neural progenitor cell

ASJC Scopus subject areas

  • General

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