Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum
Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum
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DOI：
10.1016/s0006-8993(01)02681-6
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发表时间：
2001-08-03
期刊：
影响因子：
2.9
通讯作者：
Le, WD
中科院分区：
文献类型：
--
作者：
He, Y;Appel, S;Le, WD
为了确定免疫/炎症因子在帕金森病黑质多巴胺能细胞变性中的作用，我们用体视技术检测了小鼠同侧纹状体注射6-羟多巴胺（6-OHDA）后酪氨酸羟化酶（TH）阳性免疫反应神经元数量和cd11b阳性免疫反应小胶质细胞谱。我们进一步研究了二甲胺四环素对小胶质细胞活化的抑制作用以及随后对黑质细胞的保护作用。与对侧黑质（SN）相比，注射后1-3天同侧黑质（SN）小胶质细胞的相对数量从31%增加到32%，注射后7天和14天分别增加到55%和59%。这些变化开始于第7天和第14天TH免疫反应性下降34%和42%之前。在注射6-OHDA后的第14天，与未注射二甲胺四环素的帕金森动物相比，注射二甲胺四环素的动物的小胶质细胞活化被抑制了47%，TH阳性细胞的保护率提高了21%。这些结果提示，小胶质细胞的活化可能参与了6-羟多巴胺诱导的帕金森小鼠的神经细胞退化。(C) 2001 Elsevier Science B.V.版权所有
To determine the role of immune/inflammatory factors in dopaminergic cell degeneration in parkinsonian substantia nigra, we assayed tyrosine hydroxylase (TH)-positive immunoreactive neuronal numbers with stereologic techniques and CD11b-positive immunoreactive micro-glial profiles following 6-hydroxydopamine (6-OHDA) injection into ipsilateral striatum of mice. We further investigated the effect of minocycline on the inhibition of microglial activation and subsequent protection of nigral cells. The relative number of microglial profiles in the substantia nigra (SN) ipsilateral to the injection increased from 31 to 32% 1-3 days after injection, and increased further to 55% by 7 days and 59% by 14 days, compared with the contralateral SN. These changes started prior to the decrease of TH immunoreactivity of 34% on day 7 and of 42% by day 14. In animals treated with minocycline, microglial activation was inhibited by 47%, and TH positive cells were protected by 21% at day 14 after 6-OHDA injection, compared with those parkinsonian animals without minocycline treatment. All these results suggest that microglial activation may be involved in the nigral cell degeneration in 6-OHDA induced parkinsonian mice. (C) 2001 Elsevier Science B.V. All rights reserved.