Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors.
Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors.
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DOI：
10.1186/1742-2094-10-87
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发表时间：
2013-07-18
影响因子：
9.3
通讯作者：
O'Connor JC
中科院分区：
文献类型：
--
作者：
Lawson MA;Parrott JM;McCusker RH;Dantzer R;Kelley KW;O'Connor JC
色氨酸降解酶吲哚胺-2，3-双加氧酶1（IDO 1）的激活与抑郁症行为体征的发展相关。全身免疫激发诱导外周和脑中的IDO 1，导致犬尿氨酸的循环和脑浓度增加。然而，脑内IDO 1活性是否是中枢免疫攻击后小鼠抑郁样行为表现所必需的仍有待阐明。我们研究了脑IDO 1在介导小鼠侧脑室注射生理盐水或脂多糖（LPS，10 ng）后抑郁样行为中的作用。LPS增加不动的持续时间在尾部悬挂试验和减少偏好的蔗糖溶液。这些作用与中枢IDO 1的激活有关，而与外周IDO 1的激活无关，因为LPS增加了脑犬尿氨酸，但对犬尿氨酸的血浆浓度没有影响。有趣的是，IDO 1的基因缺失或药理学抑制，使用1-甲基色氨酸，废除了减少蔗糖偏好诱导的脑室内LPS。1-甲基-色氨酸也阻断了在尾部悬挂试验期间LPS诱导的不动持续时间的增加。这些数据表明，脑IDO 1的激活足以诱导小鼠响应于中枢LPS的抑郁样行为。
Activation of the tryptophan degrading enzyme indoleamine-2,3-dioxygenase 1 (IDO1) is associated with the development of behavioral signs of depression. Systemic immune challenge induces IDO1 in both the periphery and the brain, leading to increased circulating and brain concentrations of kynurenines. However, whether IDO1 activity within the brain is necessary for the manifestation of depression-like behavior of mice following a central immune challenge remains to be elucidated. We investigated the role of brain IDO1 in mediating depression-like behavior of mice in response to intracerebroventricular injection of saline or lipopolysaccharide (LPS, 10 ng). LPS increased the duration of immobility in the tail suspension test and decreased preference for a sucrose solution. These effects were associated with an activation of central but not peripheral IDO1, as LPS increased brain kynurenine but had no effect on plasma concentrations of kynurenine. Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1-methyl-tryptophan, abrogated the reduction in sucrose preference induced by intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced increase in duration of immobility during the tail suspension test. These data indicate that activation of brain IDO1 is sufficient to induce depression-like behaviors of mice in response to central LPS.
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影响因子：
3.6
作者：
Kanai M;Funakoshi H;Takahashi H;Hayakawa T;Mizuno S;Matsumoto K;Nakamura T
通讯作者：
Nakamura T
影响因子：
10.6
作者：
Miller, Andrew H.;Maletic, Vladimir;Raison, Charles L.
通讯作者：
Raison, Charles L.
影响因子：
4.7
作者：
Kaster, Manuella P.;Gadotti, Vinicius M.;Rodrigues, Ana Lucia S.
通讯作者：
Rodrigues, Ana Lucia S.
影响因子：
15.1
作者：
Krabbe, KS;Reichenberg, A;Bruunsgaard, H
通讯作者：
Bruunsgaard, H
影响因子：
11
作者：
O'Connor, J. C.;Lawson, M. A.;Dantzer, R.
通讯作者：
Dantzer, R.