Frank Matthew G, Baratta Michael V, Sprunger David B, Watkins Linda R, Maier Steven F
Department of Psychology and Center for Neuroscience, Campus Box 345, University of Colorado, Boulder, CO 80309-0345, USA.
Brain Behav Immun. 2007 Jan;21(1):47-59. doi: 10.1016/j.bbi.2006.03.005. Epub 2006 May 2.
Prior exposure to a stressor can potentiate CNS pro-inflammatory immune responses to a peripheral immune challenge. However, the neuroimmune substrate(s) mediating this effect has not been determined. The present investigation examined whether microglia serve as this neuroimmune substrate given that microglia are the primary immune effector cell in the CNS. The effect of inescapable shock (IS) on glial activation (MHC II, CD11b, Iba-1, and GFAP) and regulatory markers (CD200) in vivo, and microglia pro-inflammatory responses (interleukin-1beta; IL-1beta) to lipopolysaccharide (LPS) ex vivo, were assessed in rat hippocampus. IS upregulated the microglia activation marker MHC II 24h post-IS, while the astroglia marker GFAP was unaffected. IS also downregulated the neuronal glycoprotein CD200, which functions to hold microglia in a quiescent state. Moreover, IS potentiated the pro-inflammatory response to LPS ex vivo 24h post-IS in isolated hippocampal microglia. Finally, the behavioral controllability of shock was manipulated and the effect of escapable (controllable) shock was comparable to the effect of IS on hippocampal microglia responses to LPS ex vivo. The present results suggest that stress can activate microglia, thereby sensitizing the pro-inflammatory reactivity of microglia to immunogenic stimuli.
先前暴露于应激源可增强中枢神经系统（CNS）对周围免疫挑战的促炎免疫反应。然而，介导这种效应的神经免疫底物尚未确定。鉴于小胶质细胞是中枢神经系统中的主要免疫效应细胞，本研究探讨了小胶质细胞是否作为这种神经免疫底物。在大鼠海马体中评估了不可逃避电击（IS）对体内胶质细胞活化（主要组织相容性复合体II类分子、CD11b、离子钙结合衔接分子1和胶质纤维酸性蛋白）和调节标志物（CD200）的影响，以及离体小胶质细胞对脂多糖（LPS）的促炎反应（白细胞介素-1β；IL-1β）。不可逃避电击后24小时上调了小胶质细胞活化标志物主要组织相容性复合体II类分子，而星形胶质细胞标志物胶质纤维酸性蛋白未受影响。不可逃避电击还下调了神经元糖蛋白CD200，其作用是使小胶质细胞保持静止状态。此外，不可逃避电击后24小时，增强了离体海马体小胶质细胞对脂多糖的促炎反应。最后，对电击的行为可控性进行了操纵，可逃避（可控）电击的效果与不可逃避电击对离体海马体小胶质细胞对脂多糖反应的效果相当。目前的结果表明，应激可激活小胶质细胞，从而使小胶质细胞对免疫原性刺激的促炎反应性敏感化。
