Department of Animal Physiology, Biology, and Biotechnology, Ruhr-University Bochum, ND/5131, D-44780 Bochum, Germany.
Parkinsons Dis. 2010 Jul 8;2010:375462. doi: 10.4061/2010/375462.
Accumulation of α-synuclein is observed in neurodegenerative diseases like Parkinson's disease and Multiple System Atrophy. In previous studies with transgenic C57BL/6 mice overexpressing α-synuclein carrying the mutations A53T and A30P found in Parkinson's disease or with a parkin-null background, we reported severe mitochondrial impairments in neurons and to a larger extent in glial cells of the mesencephalon. Neuron death was not observed in the brain. Here we show that the mice show severe motor impairments in behavioral tests. In addition, these mice exhibit astrocytic cell death in the spinal cord, accompanied by extensive gliosis and microglial activation. This is shown by cell death staining and immunohistochemistry. Ultrastructural analyses revealed severe mitochondrial impairments not only in astrocytes, but also in oligodendrocytes and, to a small extent, in neurons. Thus, the transgenic mice show a profound pathology in glial cells of the spinal cord.
α-突触核蛋白在神经退行性疾病如帕金森病和多系统萎缩中积累。在之前的研究中，我们使用过表达帕金森病中携带 A53T 和 A30P 突变的 α-突触核蛋白的转基因 C57BL/6 小鼠或 Parkin 基因敲除背景的小鼠，发现中脑神经元和在更大程度上的神经胶质细胞存在严重的线粒体损伤。在大脑中未观察到神经元死亡。在这里，我们表明这些小鼠在行为测试中表现出严重的运动障碍。此外，这些小鼠在脊髓中表现出星形胶质细胞死亡，伴有广泛的神经胶质增生和小胶质细胞激活。这通过细胞死亡染色和免疫组织化学显示。超微结构分析显示，不仅在星形胶质细胞中，而且在少突胶质细胞中，并且在一定程度上在神经元中，都存在严重的线粒体损伤。因此，转基因小鼠在脊髓的神经胶质细胞中表现出明显的病理。
