The 6-Hydroxydopamine-induced Nigrostriatal Neurodegeneration Produces Microglia-like NG2 Glial Cells in the Rat Substantia Nigra
The 6-Hydroxydopamine-induced Nigrostriatal Neurodegeneration Produces Microglia-like NG2 Glial Cells in the Rat Substantia Nigra
复制标题
DOI：
10.1002/glia.21040
复制
发表时间：
2010-11-01
期刊：
影响因子：
6.2
通讯作者：
Taniguchi, Takashi
中科院分区：
文献类型：
--
作者：
Kitamura, Yoshihisa;Inden, Masatoshi;Taniguchi, Takashi
表达神经元/神经胶质2(NG2)的细胞通常被称为少突胶质前体细胞。表达NG2的细胞也被鉴定为多能祖细胞。然而，小胶质细胞样的NG2神经胶质细胞在帕金森氏病(PD)等神经退行性疾病中尚未得到充分研究。在本研究中，我们选择了两种帕金森病大鼠模型，即黑质或纹状体内注射6-羟基多巴胺(6-OHDA)，因为构成黑质纹状体通路的多巴胺(DA)神经元的胞体在黑质致密部(SNPC)，而它们的神经末梢在纹状体。在黑质6-OHDA注射模型中，SNPC内可检测到活化的NG2阳性细胞，而纹状体中未检测到。相反，在纹状体6-OHDA注射模型中，在SNPC和纹状体都检测到这些细胞。在这两种模型中，激活的NG2阳性细胞位于SNPC中存活的酪氨酸羟化酶(TH)阳性神经元附近。此外，SNPC中被激活的NG2阳性细胞共表达小胶质细胞/巨噬细胞标志物--离子钙结合适配器分子1(IBA1)。有趣的是，这些双阳性的胶质细胞共表达胶质细胞系衍生神经营养因子(GDNF)。这些结果提示，小胶质细胞样NG2神经胶质细胞可能有助于保护DA神经元，并可能为帕金森病的治疗提供新的靶点。(C)2010年Wiley-Liss公司
Neuron/glial 2 (NG2)-expressing cells are often referred to as oligodendrocyte precursor cells. NG2-expressing cells have also been identified as multipotent progenitor cells. However, microglia-like NG2 glial cells have not been fully examined in neurodegenerative disorders such as Parkinson's disease (PD). In the present study, we chose two rat models of PD, i.e., intranigral or intrastriatal injection of 6-hydroxydopamine (6-OHDA), since the cell bodies of dopamine (DA) neurons, which form a nigrostriatal pathway, are in the substantia nigra pars compacta (SNpc) while their nerve terminals are in the striatum. In the nigral 6-OHDA-injected model, activated NG2-positive cells were detected in the SNpc but not in the striatum. In contrast, in the striatal 6-OHDA-injected model, these cells were detected in both the SNpc and the striatum. In both models, activated NG2-positive cells were located close to surviving tyrosine hydroxylase (TH)-positive neurons in the SNpc. In addition, activated NG2-positive cells in the SNpc coexpressed ionized calcium-binding adaptor molecule 1 (Iba1), a microglia/macrophage marker. Interestingly, these double-positive glial cells coexpressed glial cell line-derived neurotrophic factor (GDNF). These results suggest that microglia-like NG2 glial cells may help protect DA neurons and may lead to new therapeutic targets in PD. (C) 2010 Wiley-Liss, Inc.