Faculty of Sciences, Laboratory of Cellular and Molecular Neurosciences, University of Chile, Ñuñoa, Santiago, Chile International Center for Biomedicine (ICC), Vitacura, Santiago, Chile.
J Alzheimers Dis. 2013;37(4):849-56. doi: 10.3233/JAD-131843.
Neuroinflammation is a process related to the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Increasing sets of evidence support the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration, a process we are calling neuroimmunomodulation in AD. On the basis of the hypothesis that pathological tau aggregates induce microglial activation with the subsequent events of the neuroinflammatory cascade, we have studied the effects of tau oligomeric species and filamentous structures over microglial cells in vitro. Tau oligomers and fibrils were induced by arachidonic acid and then their actions assayed upon addition to microglial cells. We showed activation of the microglia, with significant morphological alterations as analyzed by immunofluorescence. The augmentation of nitrites and the proinflammatory cytokine IL-6 was evaluated in ELISA assays. Furthermore, conditioned media of stimulated microglia cells were exposed to hippocampal neurons generating altered patterns in these cells, including shortening of neuritic processes and cytoskeleton reorganization.
神经炎症与包括阿尔茨海默病（AD）在内的几种神经退行性疾病的发病有关。越来越多的证据支持神经胶质细胞和神经元之间相互作用模式失调在神经元变性途径中的主要作用，我们将这一过程称为 AD 中的神经免疫调节。基于病理性 tau 聚集物诱导小胶质细胞激活，随后引发神经炎症级联反应的假说，我们已经在体外研究了 tau 寡聚体和丝状结构对小胶质细胞的影响。通过花生四烯酸诱导 tau 寡聚体和原纤维的形成，然后在加入小胶质细胞后检测它们的作用。我们通过免疫荧光分析显示小胶质细胞的激活，以及显著的形态改变。通过 ELISA 检测评估亚硝酸盐和促炎细胞因子 IL-6 的增加。此外，刺激的小胶质细胞的条件培养基暴露于海马神经元中，导致这些细胞出现改变的模式，包括神经突过程缩短和细胞骨架重组。
