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

Journal of Neuroinflammation

Frédéric Calon³  Renée Bazin²  Francesca Cicchetti¹  Janelle Drouin-Ouellet¹  Isabelle Paré²  Mélanie Bousquet³  Isabelle St-Amour² 

[1] Département de Psychiatrie & Neurosciences, Faculté de Médecine, Université Laval, Québec, QC, Canada, G1V 0A6;Département de Recherche et Développement, Héma-Québec, Québec, QC, Canada , G1V 5C3;Faculté de Pharmacie, Université Laval, Québec, QC, Canada , G1V 0A6

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

Others  :  1160208
DOI  :  10.1186/1742-2094-9-234

 received in 2012-05-25, accepted in 2012-09-16,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 St-Amour et al.; licensee BioMed Central Ltd.

【 图 表 】

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