IL-1beta 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 proinflammatory cytokine IL-1beta. Administration of IL-1beta or acute stress suppressed hippocampal cell proliferation. Blockade of the IL-1beta 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-kappaB signaling pathway. These findings demonstrate that IL-1beta is a critical mediator of the antineurogenic and depressive-like behavior caused by acute and chronic stress.
Koo
Ja Wook
JW
Department of Psychology, Yale University, New Haven, CT 06520-8205, USA.
Duman
Ronald S
RS
D000818:Animals; D049109:Cell Proliferation; D003863:Depression / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D013312:Stress, Physiological / Q000378:metabolism*
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D016328:NF-kappa B