Sawada Makoto, Sawada Hirohide, Nagatsu Toshiharu
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Neurodegener Dis. 2008;5(3-4):254-6. doi: 10.1159/000113717. Epub 2008 Mar 6.
The inflammatory process in the brain, which is accompanied by changes in the levels of proinflammatory cytokines and neurotrophins, along with the presence of activated microglia, has recently gained much attention in neurodegenerative diseases. Activated microglia produce either neuroprotective or neurotoxic factors. Many reports indicate that activated microglia promote degeneration of dopamine (DA) neurons in Parkinson's disease (PD). On the other hand, there are several lines of evidence that microglia also have a neuroprotective function. Microglia activated with lipopolysaccharide in the nigrostriatum of neonatal mice protect DA neurons against the PD-producing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas activated microglia in aged mice promote DA cell death by MPTP. These results suggest that the function of activated microglia may change in vivo from neuroprotective to neurotoxic during aging as neurodegeneration progresses in the PD brain.
大脑中的炎症过程，伴随着促炎细胞因子和神经营养因子水平的变化，以及活化小胶质细胞的存在，最近在神经退行性疾病中受到了广泛关注。活化的小胶质细胞会产生神经保护因子或神经毒性因子。许多报告表明，活化的小胶质细胞会促进帕金森病（PD）中多巴胺（DA）神经元的退化。另一方面，有几条证据表明小胶质细胞也具有神经保护功能。在新生小鼠黑质纹状体中用脂多糖激活的小胶质细胞可保护DA神经元免受产生PD的神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的侵害，而老年小鼠中活化的小胶质细胞则会通过MPTP促进DA细胞死亡。这些结果表明，随着PD大脑中神经退行性变的进展，活化小胶质细胞的功能在体内可能会从神经保护转变为神经毒性。
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