Rodrigues R W P, Gomide V C, Chadi G
Laboratory of Neuroregeneration, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Int J Neurosci. 2004 Feb;114(2):197-216. doi: 10.1080/00207450490249338.
Astroglial and microglial activation were analyzed in the ventral tegmental area (VTA) in adult male Wistar rats, after an unilateral striatal 6-hydroxydopamine (6-OHDA) injection. Different doses (8, 4, and 1 microg) of 6-OHDA were injected in the left side of the neostriatum; animals were sacrificed 22 days later. Control animals received an injection of the same volume of the solvent. The tyrosine hydroxylase (TH) positive dopamine cells, the glial fibrillary acidic protein (GFAP) immuno -labeled astrocytes, and the OX42 immunoreactive microglia were visualized by means of immunohistochemistry and quantified by stereologic methods employing the optical dissector and the point intercepts. The number and the density of TH immunoreactive cell bodies were decreased by 45% and 46%, respectively, in the sampled field of the ipsilateral VTA of 8 microg 6-OHDA injected rats. The GFAP immunohistochemistry revealed in the ipsilateral VTA increases the number and density of astroglial cells (154% and 166% of control, respectively) in the rats with a higher dose of the 6-OHDA, and also in the volume fraction of the astroglial processes after 8 microg (41% of control) and 4 microg (24% of control) of 6-OHDA. Increased number (76% of control) and density (77% of control) of OX42 microglial labeled profiles and microglial processes (51% of control) were found in the ipsilateral VTA of the 8 microg 6-OHDA injected animals. These results suggest that the retrograde degeneration of the mesostriatal dopamine pathways, induced by a striatal injection of 6-OHDA, leads to astroglial and microglial reactions in the VTA. The interaction between activated glial cells may be involved in the wounding and repair events in the partial lesioned system, and also in the trophic paracrine responses in the surviving VTA dopamine neurons.
在成年雄性Wistar大鼠单侧纹状体注射6-羟基多巴胺(6-OHDA)后,对腹侧被盖区(VTA)的星形胶质细胞和小胶质细胞激活情况进行了分析。将不同剂量(8、4和1微克)的6-OHDA注射到新纹状体左侧;22天后处死动物。对照动物注射相同体积的溶剂。通过免疫组织化学观察酪氨酸羟化酶(TH)阳性多巴胺能细胞、胶质纤维酸性蛋白(GFAP)免疫标记的星形胶质细胞和OX42免疫反应性小胶质细胞,并采用光学分割器和点计数法的体视学方法进行定量。在注射8微克6-OHDA的大鼠同侧VTA的采样区域中,TH免疫反应性细胞体的数量和密度分别降低了45%和46%。GFAP免疫组织化学显示,在同侧VTA中,高剂量6-OHDA的大鼠星形胶质细胞的数量和密度增加(分别为对照的154%和166%),在注射8微克(对照的41%)和4微克(对照的24%)6-OHDA后,星形胶质细胞突起的体积分数也增加。在注射8微克6-OHDA的动物同侧VTA中,发现OX42小胶质细胞标记轮廓的数量(对照的76%)和密度(对照的77%)以及小胶质细胞突起(对照的51%)增加。这些结果表明,纹状体注射6-OHDA诱导的中脑纹状体多巴胺能通路逆行性变性导致VTA中的星形胶质细胞和小胶质细胞反应。激活的胶质细胞之间的相互作用可能参与部分损伤系统中的损伤和修复事件,也参与受损多巴胺能神经元的营养旁分泌反应。