BIOMED, Hasselt University, Agoralaan C Building, 3590 Diepenbeek, Belgium ; Neuroscience, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
Mediators Inflamm. 2013;2013:271359. doi: 10.1155/2013/271359. Epub 2013 Jul 10.
Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS) is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.
大量证据表明临床抑郁症与免疫功能改变之间存在关联。全身给予细菌脂多糖（LPS）常用于研究啮齿动物与炎症相关的行为变化。在这些实验中，我们假设外周免疫激活会导致小鼠的神经炎症和类似抑郁的行为。我们报告称，LPS 的全身给药会诱导转 GFAP-luc 小鼠的星形胶质细胞活化，并增加野生型小鼠齿状回中针对小胶质细胞标记物离子钙结合衔接分子 1 的免疫反应性。此外，LPS 处理会导致血清和大脑中的细胞因子水平强烈但短暂地增加。除了研究 LPS 诱导的神经炎症外，我们还通过在一系列行为范式中评估 LPS 处理的小鼠，来测试疾病是否可以与类似抑郁的行为分开。我们的行为数据表明，全身 LPS 给药会引起疾病和轻度类似抑郁的行为。然而，由于疾病和类似抑郁的行为在时间上重叠，且对抑郁相关行为本身的影响较小，因此在目前的啮齿动物模型中，无法将疾病与类似抑郁的行为分开。
