Role of brain transmigrating neutrophils in depression-like behavior during systemic infection
Role of brain transmigrating neutrophils in depression-like behavior during systemic infection
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DOI：
10.1038/mp.2013.137
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发表时间：
2014-05-01
影响因子：
11
通讯作者：
Luheshi, G. N.
中科院分区：
文献类型：
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作者：
Aguliar-Valles, A.;Kim, J.;Luheshi, G. N.
外周炎症诱导表达白细胞介素（IL）-1 β的中性粒细胞迁移至大脑。我们通过评估它们在与情绪障碍相关的疾病行为中的作用，研究了这提供了一种新的免疫与大脑交流途径的可能性。用脂多糖（LPS）处理的小鼠产生绝望样行为，并且施用抗多形核巧酸抗体消除LPS诱导的绝望样和不合群行为，其与脑中IL-1 β表达水平相关。这些行为变化直接由能量调节激素瘦素介导。增加内源性瘦素的浓度在肥胖加剧，而它的中和使用特定的抗血清衰减的疾病行为，重要的是中性粒细胞的迁移过程。我们的研究结果表明，外周中性粒细胞在向大脑传递炎症信号中的作用，这似乎取决于生物体的能量状态。这构成了一种与情绪障碍相关的免疫-大脑沟通的新机制。
Peripheral inflammation induces transmigration of interleukin (IL)-1 beta-expressing neutrophils to the brain. We investigated the possibility that this presents a new route of immune-to-brain communication by assessing their role in sickness behaviors relevant for mood disorders. Mice treated with lipopolysaccharide (LPS) developed despair-like behavior, and administration of an anti-polymorphonuclear antibody abolished LPS-induced despair-like and asocial behaviors, which correlated with the levels of IL-1 beta expression in the brain. These behavioral changes were directly mediated by the energy-regulating hormone, leptin. Increasing the concentration of endogenous leptin during obesity exacerbated, whereas its neutralization using a specific antiserum attenuated sickness behaviors and importantly the neutrophil transmigrating process. Our results indicate a role for peripheral neutrophils in conveying inflammatory signals to the brain, which appears to be dependent on the energy status of the organism. This constitutes a novel mechanism of immune-to-brain communication relevant to mood disorders.