Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior
Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior
复制标题
DOI：
10.1016/j.psyneuen.2007.03.005
复制
发表时间：
2007-06-01
影响因子：
3.7
通讯作者：
Castanon, Nathalie
中科院分区：
文献类型：
--
作者：
Frenois, Francois;Moreau, Maite;Castanon, Nathalie
促炎性细胞因子同时导致疾病行为和抑郁，但它们各自的神经生物学相关性仍然知之甚少。因此，本研究的目的是在小鼠中鉴定内毒素(脂多糖，830微克/公斤，腹腔注射)引起疾病和抑郁样行为的神经底物。通过在6小时(此时疾病预计最严重)或24小时(此时疾病预计最轻微且不偏向于抑郁行为的测量)的测试，将内毒素诱导的抑郁样行为与内毒素诱导的疾病分离。同时用免疫组织化学方法检测急性和慢性细胞反应性标志物(c-Fos和FosB/Delta FosB)在这两个时间点的表达。与生理盐水相比，LIDs在新笼子中的运动能力在6h时降低，但在24h时不变。相反，尾部悬吊试验中的不动持续时间在6h和24h均延长。在强迫游泳实验中，运动活动减少和抑郁样行为之间的这种分离在脂多糖后24小时得到证实。LIDS还减少了24小时和48小时的蔗糖消耗，尽管那时食物和水的消耗是正常的。内毒素诱导的抑郁样行为与特定脑结构的细胞活动延迟有关(FosB/Delta FosB免疫组织化学染色)，尤其是杏仁核、海马区和下丘脑，而c-Fos标记在内毒素后6h在所有脑区均显著减少。这些结果首次证明了构成细胞因子诱导的疾病行为和细胞因子诱导的类抑郁行为的大脑结构之间存在功能性分离，并为细胞因子对情感产生影响的神经解剖学大脑回路提供了重要线索。(C)2007爱思唯尔有限公司。保留所有权利。
Proinflammatory cytokines induce both sickness behavior and depression, but their respective neurobiological correlates are still poorly understood. The aim of the present study was therefore to identify in mice the neural substrates of sickness and depressive-like behavior induced by lipopolysaccharide (LPS, 830 mu g/kg, intraperitoneal). LPS-induced depressive-like behavior was dissociated from LPS-induced sickness by testing mice either at 6 h (at which time sickness was expected to be maximal) or at 24 h post-LPS (at which time sickness was expected to be minimal and not to bias the measurement of depressive-like behavior). Concurrently, the expression of acute and chronic cellular reactivity markers (c-Fos and FosB/Delta FosB, respectively) was mapped by immunohistochemistry at these two time points. In comparison to saline, LIDS decreased motor activity in a new cage at 6 h but not at 24 h. In contrast, the duration of immobility in the tail suspension test was increased at both 6 and 24h. This dissociation between decreased motor activity and depressive-like behavior was confirmed at 24h post-LPS in the forced swim test. LIDS also decreased sucrose consumption at 24 and 48h, despite normal food and water consumption by that time. At 24h post-LPS, LPS-induced depressive-like behavior was associated with a delayed cellular activity (as assessed by FosB/Delta FosB immunostaining) in specific brain structures, particularly within the extended amygdala, hippocampus and hypothalamus, whereas c-Fos labeling was markedly decreased by that time in all the brain areas at 6 h post-LPS. These results provide the first evidence in favor of a functional dissociation between the brain structures that underlie cytokine-induced sickness behavior and cytokine-induced depressive-like behavior, and provide important cues about the neuroanatomical brain circuits through which cytokines could have an impact on affect. (C) 2007 Elsevier Ltd. ALL rights reserved.