کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2202229 1100074 2007 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Parkinson disease IgG and C5a-induced synergistic dopaminergic neurotoxicity: Role of microglia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Parkinson disease IgG and C5a-induced synergistic dopaminergic neurotoxicity: Role of microglia
چکیده انگلیسی

Increasing evidence suggests the involvement of immune/inflammatory system in Parkinson's disease (PD). Many immune/inflammatory factors may synergistically participate in PD. In this study, we demonstrated that immunoglobulin G from the serum of 4/11 PD patients (PDIgG, 60 μg/ml) and recombinant human C5a (0.1 nM) synergistically induced selective dopaminergic neurodegeneration in rat mesencephalic neuron–glia cultures, while that PDIgG alone or C5a alone was minimally toxic or nontoxic. IgG from 17 disease controls and from 7 normal controls did not significantly induce dopaminergic neurotoxicity in the cultures even in the presence of C5a. Using mesencephalic neuron-enriched cultures, we found that the synergistic dopaminergic neurotoxicity was mediated by glia. The results from microglia-supplemented neuronal cultures, astroglia-supplemented neuronal cultures and neuron–astroglia cocultures indicated that microglia, not astroglia, played a pivotal role in the neurotoxicity. Through immunocytochemistry analysis and assay of proinflammatory factors, we observed that each of the four PDIgGs (60 μg/ml) and C5a (0.1 nM) synergistically induced microglia activation and production of superoxide and nitric oxide (NO) in neuron–glia cultures. Further investigations indicated that superoxide and NO were both responsible for the synergistic neurotoxicity. Finally, using F(ab′)2 fragments of PDIgG, we demonstrated that microglial Fc receptors may play an important role in the neurotoxicity. Our work provides new evidence for the involvement of the immune/inflammatory system in PD and helpful clues for studying the combined effect of antibody and complement on microglia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 50, Issue 1, January 2007, Pages 39–50
نویسندگان
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