Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease
Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease
复制标题
DOI：
10.1002/mds.870130205
复制
发表时间：
1998-03-01
影响因子：
8.6
通讯作者：
Blunt, SB
中科院分区：
文献类型：
--
作者：
Banati, RB;Daniel, SE;Blunt, SB
帕金森病(PD)患者黑质神经细胞死亡的原因和机制尚不清楚。关于细胞死亡是由单个事件引起的，随后是与衰老一致的细胞丢失，还是存在正在进行的病理过程，也存在争议。使用从伦敦帕金森病学会脑组织银行获得的尸检组织，我们试图确定细胞凋亡，或者更具体地说，神经元的DNA片段化，是否是黑质病理的一个显著特征。此外，我们使用高度敏感的标记物CR3/43和EBM11研究了黑质小胶质细胞的激活，作为正在进行的病理的指标。用胶质纤维酸性蛋白(GFAP)免疫染色对反应性星形胶质细胞进行评估。对10例经病理证实的帕金森病患者进行了研究。在所有病例中，无论患者的病程、严重程度、药物治疗或年龄如何，通过使用生物素化dUTP和末端脱氧核苷酸转移酶(TDT)对DNA片段进行原位末端标记，均未发现黑质细胞凋亡的证据。相比之下，多系统萎缩(MSA)病例作为该技术的阳性对照。在这种情况下，可以在脑干的神经元和非神经元细胞中发现阳性的DNA末端标记。然而，在帕金森病患者中，激活的小胶质细胞的CR3/43和EBM11标记显示黑质有局限性的病理改变。这一过程似乎与病程无关，即使在严重神经元丢失的患者中也是如此。神经胶质细胞的激活在多大程度上反映了黑质的进行性病理，以及那些与体内显著的神经细胞凋亡相关的因素，如神经营养因子剥夺，是否是帕金森病黑质神经元丢失的主要原因，仍有待确定。未来的研究应该集中在新近发病的帕金森病或偶发性路易体病上，以进一步解决这些问题。
The cause and mechanism of neuronal cell death in the substantia nigra of patients with Parkinson's disease (PD) are unknown. There is also controversy about whether the cell death results from a single event followed by cell loss consistent with aging or whether there is an ongoing pathologic process. Using postmortem tissue obtained from the Parkinson's Disease Society Brain Tissue Bank in London, we have sought to establish whether apoptosis, or more specifically DNA fragmentation of neurons, is a prominent feature of nigral pathology. In addition, we have studied microglial activation in the substantia nigra as an indicator of ongoing pathology using the highly sensitive markers CR3/43 and EBM11. Reactive astrocytes have been assessed using immunostaining for glial fibrillary acidic protein (GFAP). Ten patients with pathologically proven PD were studied. In all cases, regardless of disease duration, severity, drug treatment, or age of the patient, there was no evidence of apoptosis in the substantia nigra as assessed by in situ end-labeling of DNA fragments using biotinylated dUTP and terminal deoxynucleotidyl transferase (TdT). In contrast, a case of multiple system atrophy (MSA) served as a positive control for the technique. In this case, positive DNA end-labeling could be found in neurons and non-neuronal cells in the brain stem. In the PD cases, there was, however, localized pathology in the substantia nigra as revealed by the CR3/43 and EBM11 markers for activated microglia. This process seemed independent of disease duration and was florid even in patients with severe neuronal loss. It remains to be determined to what extent the activation of glial cells reflects progressive nigral pathology, and whether those factors which are classically associated with prominent apoptotic neuronal cell death in vivo, such as neurotrophic factor deprivation, are prime causes of nigral neuronal loss in PD. Future studies should focus on recent-onset PD or incidental Lewy body disease to further address these questions.