Mirza B, Hadberg H, Thomsen P, Moos T
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark.
Neuroscience. 2000;95(2):425-32. doi: 10.1016/s0306-4522(99)00455-8.
Virtually any neurological disorder leads to activation of resident microglia and invasion of blood-borne macrophages, which are accompanied by an increase in number and change in phenotype of astrocytes, a phenomenon generally termed reactive astrocytosis. One of the functions attributed to activation of astrocytes is thought to involve restoration of tissue damage. Hitherto, the role of astrocytes in the inflammatory reaction occurring in Parkinson's disease has not received much attention. In the present study, we examined the inflammatory events in autopsies of the substantia nigra and putamen from Parkinson's disease patients using age-matched autopsies from normal patients as controls. In the substantia nigra, activation of microglia was consistently observed in all Parkinson's disease autopsies as verified from immunohistochemical detection of CR3/43 and ferritin. Activation of resident microglia was not observed in the putamen. No differences were observed between controls and Parkinson's disease autopsies from the substantia nigra and putamen, in terms of distribution, cellular density or cellular morphology of astrocytes stained for glial fibrillary acidic protein or metallothioneins I and II, the latter sharing high affinity for metal ions and known to be induced in reactive astrocytes, possibly to exert anti-oxidative effects. Together, these findings indicate that the inflammatory process in Parkinson's disease is characterized by activation of resident microglia without reactive astrocytosis, suggesting that the progressive loss of dopaminergic neurons in Parkinson's disease is an ongoing neurodegenerative process with a minimum of involvement of the surrounding nervous tissue. The absence of reactive astrocytosis in Parkinson's disease contrasts what follows in virtually any other neurological disorder and may indicate that the inflammatory process in Parkinson's disease is a unique phenomenon.
几乎任何神经系统疾病都会导致常驻小胶质细胞的激活以及血源性巨噬细胞的侵入，同时伴有星形胶质细胞数量的增加和表型的改变，这一现象通常被称为反应性星形胶质细胞增生。星形胶质细胞激活的功能之一被认为与组织损伤的修复有关。迄今为止，星形胶质细胞在帕金森病炎症反应中的作用尚未受到太多关注。在本研究中，我们以年龄匹配的正常患者尸检组织作为对照，对帕金森病患者黑质和壳核的尸检组织中的炎症事件进行了检查。在黑质中，通过免疫组化检测CR3/43和铁蛋白证实，在所有帕金森病尸检组织中均持续观察到小胶质细胞的激活。在壳核中未观察到常驻小胶质细胞的激活。在黑质和壳核中，针对胶质纤维酸性蛋白或金属硫蛋白I和II染色的星形胶质细胞，在分布、细胞密度或细胞形态方面，对照组与帕金森病尸检组织之间未观察到差异，金属硫蛋白I和II对金属离子具有高亲和力，已知在反应性星形胶质细胞中被诱导产生，可能发挥抗氧化作用。总之，这些发现表明帕金森病的炎症过程以常驻小胶质细胞的激活为特征，而无反应性星形胶质细胞增生，这表明帕金森病中多巴胺能神经元的渐进性丧失是一个持续的神经退行性过程，周围神经组织的参与最少。帕金森病中缺乏反应性星形胶质细胞增生与几乎任何其他神经系统疾病的情况形成对比，这可能表明帕金森病的炎症过程是一种独特的现象。
