Possible Involvement of Complement Factor C1q in the Clearance of Extracellular Neuromelanin From the Substantia Nigra in Parkinson Disease
Possible Involvement of Complement Factor C1q in the Clearance of Extracellular Neuromelanin From the Substantia Nigra in Parkinson Disease
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DOI：
10.1097/nen.0b013e31820805b9
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发表时间：
2011-02-01
影响因子：
3.2
通讯作者：
Hoeglinger, Guenter U.
中科院分区：
文献类型：
--
作者：
Depboylu, Candan;Schaefer, Martin K. -H.;Hoeglinger, Guenter U.
补体系统的激活促进病原体和组织损伤产物从脑中的去除，并且还可能涉及神经变性疾病中的神经元细胞死亡。在这里，我们分析了C1q的表达，经典的补体级联反应的初始识别子组件，在黑质Pars延髓（SNc）在帕金森病（PD）和对照组的情况下，使用免疫组织化学和原位杂交。小胶质细胞被确定为在SNc和其他脑区中表达C1q的唯一细胞。在PD病例的SNc中，由于多巴胺能神经元变性，实质中细胞外神经黑色素沉积增加。神经黑色素颗粒和水泡的退化神经元似乎调理C1q和吞噬C1q阳性的小胶质细胞和巨噬细胞在实质和血管周围的空间。载有神经黑素的C1q阳性细胞也附着在PD的SNc血管的管腔表面。因此，我们提出的证据表明，小胶质细胞能够吞噬和清除细胞碎片的退化神经元的SNc通过C1q介导的途径在PD。
Activation of the complement system promotes the removal of pathogens and tissue damage products from the brain and may also be involved in neuronal cell death in neurodegenerative diseases. Here, we analyzed the expression of C1q, the initial recognition subcomponent of the classic complement cascade, in the substantia nigra pars compacta (SNc) in Parkinson disease (PD) and control cases using immunohistochemistry and in situ hybridization. Microglia were determined to be the only cells that expressed C1q in the SNc and other brain areas. In the SNc of PD cases, there was increased deposition of extracellular neuromelanin in the parenchyma, resulting from degeneration of dopaminergic neurons. Neuromelanin granules and blebs of degenerated neurons seemed to be opsonized by C1q and phagocytosed by C1q-positive microglia and macrophages in the parenchyma and in the perivascular spaces. Neuromelanin-laden C1q-positive cells were also attached to the luminal surfaces of blood vessels in the SNc in PD. Thus, we present evidence suggesting that microglia are capable of phagocytosing and clearing cellular debris of degenerating neurons from the SNc through a C1q-mediated pathway in PD.