La maladie de Parkinson au Canada (serveur d'exploration)

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

Identifieur interne : 001213 ( Main/Exploration ); précédent : 001212; suivant : 001214

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

Auteurs : Isabelle St-Amour ; Mélanie Bousquet ; Isabelle Paré ; Janelle Drouin-Ouellet ; Francesca Cicchetti ; Renée Bazin ; Frédéric Calon

Source :

RBID : PMC:3520736

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.


Url:
DOI: 10.1186/1742-2094-9-234
PubMed: 23046563
PubMed Central: 3520736


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<p>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
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/CD8
<sup>+</sup>
ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (
<italic>P</italic>
 < 0.01), as well as 33% and 40% reductions in the number of nigral dopaminergic neurons (
<italic>P</italic>
 < 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 (
<italic>P</italic>
 < 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.</p>
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