INSERM UMR_S975, Université Pierre et Marie Curie Paris 06 UMR_S975, CNRS UMR 7225, CR-ICM, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.
Sci Rep. 2013;3:1393. doi: 10.1038/srep01393.
In mammalians, toll-like receptors (TLR) signal-transduction pathways induce the expression of a variety of immune-response genes, including inflammatory cytokines. It is therefore plausible to assume that TLRs are mediators in glial cells triggering the release of cytokines that ultimately kill DA neurons in the substantia nigra in Parkinson disease (PD). Accordingly, recent data indicate that TLR4 is up-regulated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in a mouse model of PD. Here, we wished to evaluate the role of TLR4 in the acute mouse MPTP model of PD: TLR4-deficient mice and wild-type littermates control mice were used for the acute administration way of MPTP or a corresponding volume of saline. We demonstrate that TLR4-deficient mice are less vulnerable to MPTP intoxication than wild-type mice and display a decreased number of Iba1+ and MHC II+ activated microglial cells after MPTP application, suggesting that the TLR4 pathway is involved in experimental PD.
在哺乳动物中， toll 样受体（TLR）信号转导途径诱导多种免疫反应基因的表达，包括炎症细胞因子。因此，可以假设 TLR 是胶质细胞中触发细胞因子释放的介质，这些细胞因子最终会导致帕金森病（PD）中黑质 DA 神经元死亡。相应地，最近的数据表明，TLR4 在帕金森病小鼠模型中被 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理上调。在这里，我们希望评估 TLR4 在急性小鼠 MPTP 帕金森病模型中的作用：使用 TLR4 缺陷型小鼠和野生型同窝对照小鼠进行 MPTP 的急性给药或相应体积的生理盐水。我们证明，TLR4 缺陷型小鼠比野生型小鼠对 MPTP 中毒的敏感性更低，并且在 MPTP 应用后 Iba1+和 MHC II+激活的小胶质细胞数量减少，表明 TLR4 途径参与了实验性 PD。
