title: Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson's disease.
abstract: Intravenous immunoglobulin (IVIg) is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson's disease (PD), we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice received four injections of MPTP (15 mg/kg) at 2-hour intervals followed by a 14-day IVIg treatment, which induced key immune-related changes such as increased regulatory T-cell population and decreased CD4(+)/CD8(+) ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (P < 0.01), as well as 33% and 40% reductions in the number of nigral dopaminergic neurons (P < 0.001) in controls and IVIg-treated mice, respectively. Two-way analyses of variance further revealed lower striatal tyrosine hydroxylase protein levels, striatal homovanillic acid concentrations and nigral dopaminergic neurons (P < 0.05) in IVIg-treated animals. Collectively, our results fail to support a neurorestorative effect of IVIg on the nigrostriatal system in the MPTP-treated mice and even suggest a trend toward a detrimental effect of IVIg on the dopaminergic system. These preclinical data underscore the need to proceed with caution before initiating clinical trials of IVIg in PD patients.
authors.affiliation: Centre de Recherche du CHUL, Axe Neurosciences, T2-05, 2705, boulevard Laurier, Québec, QC, Canada, G1V 4G2.
authors.forename: Isabelle
authors.initials: I
authors.lastname: St-Amour
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bousquet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Paré
authors.forename: Janelle
authors.initials: J
authors.lastname: Drouin-Ouellet
authors.forename: Francesca
authors.initials: F
authors.lastname: Cicchetti
authors.forename: Renée
authors.initials: R
authors.lastname: Bazin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Calon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007107:Immune System / Q000187:drug effects*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D050483:Dopamine Plasma Membrane Transport Proteins; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine