Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson's disease
(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.
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- author
- St-Amour, Isabelle ; Bousquet, Mélanie ; Paré, Isabelle ; Drouin-Ouellet, Janelle LU ; Cicchetti, Francesca ; Bazin, Renée and Calon, Frédéric
- organization
- publishing date
- 2012-10-09
- 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
- article number
- 234
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:84870899667
- pmid:23046563
- 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
- 2024-02-03 04:39:11
@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 < 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.</p>}},
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}},
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}},
language = {{eng}},
month = {{10}},
publisher = {{BioMed Central (BMC)}},
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}},
doi = {{10.1186/1742-2094-9-234}},
volume = {{9}},
year = {{2012}},
}