Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice.
Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice.
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胰岛素样生长因子I的中央给药可降低小鼠的抑郁样行为和脑细胞因子表达。
DOI：
10.1186/1742-2094-8-12
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发表时间：
2011-02-09
影响因子：
9.3
通讯作者：
McCusker RH
中科院分区：
文献类型：
--
作者：
Park SE;Dantzer R;Kelley KW;McCusker RH
外源性胰岛素样生长因子(IGF)- 1在啮齿动物抑郁症模型中具有抗抑郁特性。然而，igf - 1在炎症期间的抗抑郁特性尚不清楚，也不清楚igf - 1在先天免疫系统激活后改变行为的机制。我们假设中枢igf - 1会在炎症反应的背景下减少抑郁样行为，并且它会通过诱导脑源性神经营养因子（BDNF）的表达而减少大脑中促炎细胞因子的表达来做到这一点。将igf -1 （1000 ng）注入CD-1小鼠脑室内。小鼠随后给予脂多糖灌胃（LPS, 10 ng）。评估疾病和抑郁样行为，然后分析大脑稳态mRNA表达。中枢性LPS引起小鼠典型的短暂性疾病症状，包括体重减轻、采食量减少和对新幼崽的社会探索减少。同样，LPS增加了尾悬试验（TST）的静止时间。用igf - 1或抗抑郁药进行预处理，无论LPS存在与否，都能显著减少TST中静止不动的持续时间。为了阐明IGF-I抗抑郁作用的机制，我们使用实时RT-PCR定量了全脑炎症介质的稳态mRNA表达。炎症标志物白介素-1ß （IL-1ß）、肿瘤坏死因子- α (TNF)α、诱导型一氧化氮合酶（iNOS）和胶质原纤维酸性蛋白（GFAP）表达升高，igf -1表达降低。此外，igf - 1增加了BDNF的表达。这些结果表明，igf - 1下调胶质细胞的激活，并诱导具有抗抑郁活性的内源性生长因子的表达。igf - 1的这些作用与它减少抑郁样行为的能力是平行的。
Exogenous administration of insulin-like growth factor (IGF)-I has anti-depressant properties in rodent models of depression. However, nothing is known about the anti-depressant properties of IGF-I during inflammation, nor have mechanisms by which IGF-I alters behavior following activation of the innate immune system been clarified. We hypothesized that central IGF-I would diminish depressive-like behavior on a background of an inflammatory response and that it would do so by inducing expression of the brain-derived neurotrophic factor (BDNF) while decreasing pro-inflammatory cytokine expression in the brain. IGF-I (1,000 ng) was administered intracerebroventricularly (i.c.v.) to CD-1 mice. Mice were subsequently given lipopolysaccharide i.c.v. (LPS, 10 ng). Sickness and depressive-like behaviors were assessed followed by analysis of brain steady state mRNA expression. Central LPS elicited typical transient signs of sickness of mice, including body weight loss, reduced feed intake and decreased social exploration toward a novel juvenile. Similarly, LPS increased time of immobility in the tail suspension test (TST). Pretreatment with IGF-I or antidepressants significantly decreased duration of immobility in the TST in both the absence and presence of LPS. To elucidate the mechanisms underlying the anti-depressant action of IGF-I, we quantified steady-state mRNA expression of inflammatory mediators in whole brain using real-time RT-PCR. LPS increased, whereas IGF-I decreased, expression of inflammatory markers interleukin-1ß (IL-1ß), tumor necrosis factor-(TNF)α, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP). Moreover, IGF-I increased expression of BDNF. These results indicate that IGF-I down regulates glial activation and induces expression of an endogenous growth factor that shares anti-depressant activity. These actions of IGF-I parallel its ability to diminish depressive-like behavior.
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影响因子：
2.7
作者：
Duman, Catharine H.;Schlesinger, Lee;Terwilliger, Rosemarie;Russell, David S.;Newton, Samuel S.;Duman, Ronald S.
通讯作者：
Duman, Ronald S.
影响因子：
3.9
作者：
Abdulla, D;Goralski, KB;Renton, KW
通讯作者：
Renton, KW
影响因子：
10.6
作者：
Harrison NA;Brydon L;Walker C;Gray MA;Steptoe A;Critchley HD
通讯作者：
Critchley HD
影响因子：
1.7
作者：
Dantzer, R;Gheusi, G;Kelley, KW
通讯作者：
Kelley, KW
影响因子：
7.6
作者：
Godbout, Jonathan P.;Moreau, Maite;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.