He Y, Appel S, Le W
Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Brain Res. 2001 Aug 3;909(1-2):187-93. doi: 10.1016/s0006-8993(01)02681-6.
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 microglial 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.
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，我们采用体视学技术检测了向小鼠同侧纹状体注射6-羟基多巴胺（6-OHDA）后酪氨酸羟化酶（TH）阳性免疫反应性神经元数量以及CD11b阳性免疫反应性小胶质细胞形态。我们进一步研究了米诺环素对小胶质细胞激活的抑制作用以及对黑质细胞的后续保护作用。与对侧黑质相比，注射侧黑质中小胶质细胞形态的相对数量在注射后1-3天从31%增加到32%，到7天时进一步增加到55%，到14天时增加到59%。这些变化在第7天TH免疫反应性降低34%以及第14天降低42%之前就开始了。与未用米诺环素治疗的帕金森病动物相比，在注射6-OHDA后14天，用米诺环素治疗的动物中小胶质细胞激活受到47%的抑制，TH阳性细胞受到21%的保护。所有这些结果表明，小胶质细胞激活可能参与了6-OHDA诱导的帕金森病小鼠的黑质细胞变性。
