IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress
Stress decreases neurogenesis in the adult hippocampus, and blockade of this effect is required for the actions of antidepressants in behavioral models of depression. However, the mechanisms underlying these effects of stress have not been identified. Here, we demonstrate an essential role for the p...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 2; pp. 751 - 756 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
National Academy of Sciences
15.01.2008
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Stress decreases neurogenesis in the adult hippocampus, and blockade of this effect is required for the actions of antidepressants in behavioral models of depression. However, the mechanisms underlying these effects of stress have not been identified. Here, we demonstrate an essential role for the proinflammatory cytokine IL-1β. Administration of IL-1β or acute stress suppressed hippocampal cell proliferation. Blockade of the IL-1β receptor, IL-1RI, by using either an inhibitor or IL-1RI null mice blocks the antineurogenic effect of stress and blocks the anhedonic behavior caused by chronic stress exposure. In vivo and in vitro studies demonstrate that hippocampal neural progenitor cells express IL-1RI and that activation of this receptor decreases cell proliferation via the nuclear factor-κB signaling pathway. These findings demonstrate that IL-1β is a critical mediator of the antineurogenic and depressive-like behavior caused by acute and chronic stress. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved November 16, 2007 Author contributions: J.W.K. and R.S.D. designed research; J.W.K. performed research; J.W.K. analyzed data; and J.W.K. and R.S.D. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0708092105 |