Advanced

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

St-Amour, Isabelle; Bousquet, Mélanie; Paré, Isabelle; Drouin-Ouellet, Janelle LU ; Cicchetti, Francesca; Bazin, Renée and Calon, Frédéric (2012) In Journal of Neuroinflammation 9.
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Analysis of Variance, Animals, Antigens, CD4, Antigens, CD8, Body Weight, Brain, Disease Models, Animal, Dopamine, Dopamine Plasma Membrane Transport Proteins, Dopaminergic Neurons, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immune System, Immunoglobulins, Intravenous, Immunologic Factors, MPTP Poisoning, Male, Mice, Mice, Inbred C57BL, Spleen, T-Lymphocytes, Regulatory, Tyrosine 3-Monooxygenase, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Neuroinflammation
volume
9
publisher
BioMed Central
external identifiers
  • scopus:84870899667
ISSN
1742-2094
DOI
10.1186/1742-2094-9-234
language
English
LU publication?
no
id
688ebda8-ce7d-4f42-bc80-b07e0d04287e
date added to LUP
2016-11-22 09:04:01
date last changed
2017-01-01 08:40:19
@article{688ebda8-ce7d-4f42-bc80-b07e0d04287e,
  abstract     = {<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(+)/CD8(+) ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (P &lt; 0.01), as well as 33% and 40% reductions in the number of nigral dopaminergic neurons (P &lt; 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 &lt; 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>},
  articleno    = {234},
  author       = {St-Amour, Isabelle and Bousquet, Mélanie and Paré, Isabelle and Drouin-Ouellet, Janelle and Cicchetti, Francesca and Bazin, Renée and Calon, Frédéric},
  issn         = {1742-2094},
  keyword      = {Analysis of Variance,Animals,Antigens, CD4,Antigens, CD8,Body Weight,Brain,Disease Models, Animal,Dopamine,Dopamine Plasma Membrane Transport Proteins,Dopaminergic Neurons,Enzyme-Linked Immunosorbent Assay,Flow Cytometry,Immune System,Immunoglobulins, Intravenous,Immunologic Factors,MPTP Poisoning,Male,Mice,Mice, Inbred C57BL,Spleen,T-Lymphocytes, Regulatory,Tyrosine 3-Monooxygenase,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {10},
  publisher    = {BioMed Central},
  series       = {Journal of Neuroinflammation},
  title        = {Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson's disease},
  url          = {http://dx.doi.org/10.1186/1742-2094-9-234},
  volume       = {9},
  year         = {2012},
}