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Stress, cytokines, and neural plasti...

Yale University.

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Stress, cytokines, and neural plasticity in depression: IL-1beta is an essential mediator of the anti-neurogenic and anhedonic effects of stress.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Stress, cytokines, and neural plasticity in depression: IL-1beta is an essential mediator of the anti-neurogenic and anhedonic effects of stress./
作者:	Koo, Ja Wook.
面頁冊數:	162 p.
附註:	Adviser: Ronald S. Duman.
Contained By:	Dissertation Abstracts International69-05B.
標題:	Biology, Neuroscience. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3317146
ISBN:	9780549658900

Stress, cytokines, and neural plasticity in depression: IL-1beta is an essential mediator of the anti-neurogenic and anhedonic effects of stress.
Koo, Ja Wook.

Stress, cytokines, and neural plasticity in depression: IL-1beta is an essential mediator of the anti-neurogenic and anhedonic effects of stress. - 162 p.

Adviser: Ronald S. Duman.

Thesis (Ph.D.)--Yale University, 2008.

Depression is a very serious mental illness that affects nearly 20 percent of the US population and results in enormous personal suffering and socioeconomic burden. A major contributing factor to depression is uncontrollable stress, which can precipitate or exacerbate depression. Stress-induced reduction of hippocampal neurogenesis has been extensively investigated, based on the idea that the therapeutic effects of antidepressants involve a reversal of the stress-induced hippocampal impairment. However, the mechanisms underlying the anti-neurogenic and behavioral actions of stress to pathophysiology of depression remain ill defined. One possibility is interleukin (IL)-1beta, which is a pro-inflammatory cytokine that has been implicated as a mediator of stress and a causative factor in emotional disorders, including depression and anxiety. In chapter 2, I demonstrate that IL-1beta underlies the anti-neurogenic effects of stress. Both acute and chronic stress suppressed hippocampal neurogenesis, of which the down-regulation was blocked by pre-administration of IL-1 receptor antagonist (Ra). The role of IL-1beta in the anti-neurogenic actions of acute and chronic stress was further confirmed in mice with a null mutation of the only effective IL-1beta receptor, IL-1RI. In chapter 3, I show a role of IL-1beta in the anhedonic effects of chronic unpredictable stress (CUS). The pharmacological and genetic inactivation of IL-1RI blocked the anhedonic behavior resulting from CUS. Furthermore, I charaterized the role of IL-1beta in anxiety and fear models with IL-1RI null mice, which revealed that the IL-1beta/IL-1RI system may directly influence anxiety and fear memory formation. In chapter 4, I explore the mechanisms underlying the anti-proliferative actions of IL-1beta using cultured rat adult hippocampal progenitors. I found that that IL-1beta and IL-1Ra act on cell proliferation via the IL-1R1 expressed on the neural progenitors. The anti-proliferative action of IL-1beta occurs through regulating the cell cycle, in particular, the expression of cyclin D1 and through activation of the nuclear factor-kappaB pathway in adult hippocampal progenitors. Taken together, my findings demonstrate that IL-1beta is a key mediator of stress on adult hippocampal neurogenesis and depression-related behaviors.

ISBN: 9780549658900Subjects--Topical Terms:

1017680
Biology, Neuroscience.

Stress, cytokines, and neural plasticity in depression: IL-1beta is an essential mediator of the anti-neurogenic and anhedonic effects of stress.
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