Nadjar Agnès, Bluthé Rose-Marie, May Michael J, Dantzer Robert, Parnet Patricia
UMR INRA I 244-CNRS-Université Victor Segalen Bordeaux II, Institut François Magendie, rue Léo Saignat Bordeaux, Cedex, France.
Neuropsychopharmacology. 2005 Aug;30(8):1492-9. doi: 10.1038/sj.npp.1300755.
The behavioral effects of peripherally administered interleukin-1beta (IL-1beta) are mediated by the production of cytokines and other proinflammatory mediators at the level of the blood-brain interface and by activation of neural pathway. To assess whether this action is mediated by NFkappaB activation, rats were injected into the lateral ventricle of the brain with a specific inhibitor of NFkappaB activation, the NEMO Binding Domain (NBD) peptide that has been shown previously to abolish completely IL-1beta-induced NFkappaB activation and Cox-2 synthesis in the brain microvasculature. NFkappaB pathway inactivation significantly blocked the behavioral effects of intraperitoneally administered IL-1beta in the form of social withdrawal and decreased food intake, and dramatically reduced IL-1beta-induced c-Fos expression in various brain regions as paraventricular nucleus, supraoptic nucleus, and lateral part of the central amygdala. These findings strongly support the hypothesis that IL-1beta-induced NFkappaB activation at the blood-brain interface is a crucial step in the transmission of immune signals from the periphery to the brain that underlies further events responsible of sickness behavior.
外周给予白细胞介素-1β（IL-1β）的行为效应是由血脑界面处细胞因子和其他促炎介质的产生以及神经通路的激活介导的。为了评估这种作用是否由NFκB激活介导，将大鼠脑侧脑室注射NFκB激活的特异性抑制剂——NEMO结合域（NBD）肽，先前已证明该肽可完全消除脑微血管中IL-1β诱导的NFκB激活和Cox-2合成。NFκB途径失活显著阻断了腹腔注射IL-1β以社交退缩和食物摄入量减少形式表现出的行为效应，并显著降低了IL-1β诱导的室旁核、视上核和中央杏仁核外侧部分等各个脑区的c-Fos表达。这些发现有力地支持了以下假设：血脑界面处IL-1β诱导的NFκB激活是免疫信号从外周传递到大脑的关键步骤，而这是导致疾病行为的后续事件的基础。
