Nuclear factor-κB is a critical mediator of stress-impaired neurogenesis and depressive behavior
- Ja Wook Koo a , b ,
- Scott J. Russo b ,
- Deveroux Ferguson b ,
- Eric J. Nestler b , and
- Ronald S. Duman a , 1
- aLaboratory of Molecular Psychiatry, Center for Genes and Behavior, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06519; and
- bFishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029
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Edited* by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved December 28, 2009 (received for review September 16, 2009)
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 previously undescribed therapeutical targets for depression.
Footnotes
- 1To whom correspondence should be addressed. E-mail: ronald.duman{at}yale.edu.
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Author contributions: J.W.K., E.J.N., and R.S.D. designed research; J.W.K., S.J.R., and D.F. performed research; J.W.K. and R.S.D. analyzed data; and J.W.K., S.J.R., E.J.N., and R.S.D. wrote the paper.
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The authors declare no conflict of interest.
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↵*This Direct Submission article had a prearranged editor.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0910658107/DCSupplemental.
