Open Access Research

Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson’s disease

Isabelle St-Amour123, Mélanie Bousquet12, Isabelle Paré3, Janelle Drouin-Ouellet14, Francesca Cicchetti14, Renée Bazin23 and Frédéric Calon12*

Author Affiliations

1 Centre de Recherche du CHUL (CHUQ), Axe Neurosciences, T2-05, 2705, boulevard Laurier, Québec, QC, Canada , G1V 4G2

2 Faculté de Pharmacie, Université Laval, Québec, QC, Canada , G1V 0A6

3 Département de Recherche et Développement, Héma-Québec, Québec, QC, Canada , G1V 5C3

4 Département de Psychiatrie & Neurosciences, Faculté de Médecine, Université Laval, Québec, QC, Canada, G1V 0A6

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Journal of Neuroinflammation 2012, 9:234  doi:10.1186/1742-2094-9-234

Published: 9 October 2012

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.

Keywords:
Intravenous immunoglobulin; Parkinson’s disease; Immunity; Neurodegeneration; MPTP; Dopamine