Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
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DOI：
10.1016/s0162-3109(98)00022-8
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发表时间：
1998-06-01
期刊：
影响因子：
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通讯作者：
Czlonkowska, A
中科院分区：
文献类型：
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作者：
Kohutnicka, M;Lewandowska, E;Czlonkowska, A
我们研究了1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP），多巴胺能黑质纹状体神经元的选择性神经毒素处理小鼠的神经胶质细胞的反应。多巴胺能神经元的损伤迹象在MPTP给药后第1天开始，并进展至观察时间结束（第21天）。从第1天到第14天，在黑质（SN）和纹状体中表现出短暂的小胶质细胞反应。细胞数量增加，形态改变。在超微结构水平上，观察到吞噬作用的迹象和指示生物活性物质分泌的特征。星形细胞增多在小胶质细胞反应后一天出现，并一直持续到观察时间结束。在第2天和第3天，在SN中的小胶质细胞和星形胶质细胞内观察到白细胞介素-6免疫反应性。MPTP与帕吉林（一种防止MPTP神经毒性的单胺氧化酶-B抑制剂）同时给药后，没有多巴胺能细胞耗竭或神经胶质活化的迹象。我们的研究表明，小胶质细胞和星形胶质细胞参与了MPTP给药后黑质纹状体系统的病理过程。MPTP单独不负责神经胶质细胞活化，但其代谢产物MPP+和/或受损神经元释放的药物可能参与这一过程。(C)1998 Elsevier Science B. V.保留所有权利。
We have studied the reaction of glial cells in mice treated with an intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective neurotoxin of dopaminergic nigrostriatal neurons. Signs of injury to the dopaminergic neurons started on the Ist day after MPTP administration and progressed up to the end of the observation time (21st day). A transient microglial reaction was demonstrated from the Ist until the 14th day in the substantia nigra (SN) and striatum. The cells showed an increase in number and changes in morphology. At the ultrastructural level, signs of phagocytosis and features indicating the secretion of biologically active substances were observed. Astrocytosis followed the microglial reaction by one day and was noticed until the end of the observation time. Interleukin-6 immunoreactivity was observed within microglia and astrocytes in the SN on days 2 and 3. There were no signs of depletion of dopaminergic cells or glial activation after the administration of MPTP simultaneously with pargyline, an inhibitor of monoamine oxidase-B that prevents MPTP neurotoxicity. Our study indicates that microglia and astrocytes are involved in the pathological process in the nigrostriatal system following MPTP administration. MPTP alone is not responsible for glial cell activation but its metabolite MPP+ and/or agents released by injured neurons may participate in this process. (C) 1998 Elsevier Science B.V. All rights reserved.