title: Involvement of the Fc gamma receptor in a chronic N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of dopaminergic loss.
abstract: 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 Fcγ receptors, which are critical for activation of macrophages/microglia by binding to IgGs, is also protective in this protracted model. FcγR-deficient mice display improved behavior and impaired microglial activation. Interestingly, however, Rag2 mutant but not FcγR-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.
authors.affiliation: Department of Cellular Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Arman
authors.initials: A
authors.lastname: Lira
authors.affiliation: Institute of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada, and.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kulczycki
authors.affiliation: Department of Cellular Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: Slack
authors.affiliation: Institute of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada, and.
authors.forename: Hymie
authors.initials: H
authors.lastname: Anisman
authors.affiliation: Department of Cellular Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada,; Department of Cogno-Mechatronics Engineering, Pusan National University, Korea. Electronic address: dpark@uottawa.ca.
authors.forename: David S
authors.initials: DS
authors.lastname: Park
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020267:MPTP Poisoning / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009498:Neurotoxins / Q000009:adverse effects* / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D009498:Neurotoxins; C499308:Rag2 protein, mouse; D017452:Receptors, IgG; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine