| First Author | Lira A | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 33 | Pages | 28783-93 |
| PubMed ID | 21693708 | Mgi Jnum | J:175922 |
| Mgi Id | MGI:5287935 | Doi | 10.1074/jbc.M111.244830 |
| Citation | Lira A, et al. (2011) Involvement of the Fc{gamma} Receptor in a Chronic N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mouse Model of Dopaminergic Loss. J Biol Chem 286(33):28783-93 |
| abstractText | Although there is growing evidence for a role of the innate immune response in Parkinson's disease, the nature of any humoral response in dopaminergic degeneration is uncertain. Here we report on a protracted N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of dopaminergic death that potentially allows a more full adaptive humoral response to develop. Rag2 mutant mice that lack the full adaptive response (deficient in both T and B cells) are resistant to dopaminergic death and behavioral deficiencies in this model. These mice are resensitized after reconstitution with WT splenocytes. To more directly provide evidence for humoral/IgG involvement, we show that deficiency of Fcgamma receptors, which are critical for activation of macrophages/microglia by binding to IgGs, is also protective in this protracted model. FcgammaR-deficient mice display improved behavior and impaired microglial activation. Interestingly, however, Rag2 mutant but not FcgammaR-deficient mice are resistant to a more standard N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine paradigm where death is more rapid. Taken together, these data indicate that, provided sufficient time, the humoral arm of the adaptive immune system can play a critical functional role in modulating the microglial response to dopaminergic degeneration and suggest that this humoral component may participate in degeneration in Parkinson's disease. |
