Cargando…

Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease and results from the loss of dopaminergic neurons of the nigrostriatal pathway. The pathogenesis of PD is poorly understood, but inflammatory processes have been implicated. Indeed increases in the number of major hist...

Descripción completa

Detalles Bibliográficos
Autores principales: Martin, Heather L., Santoro, Matteo, Mustafa, Sarah, Riedel, Gernot, Forrester, John V., Teismann, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855685/
https://www.ncbi.nlm.nih.gov/pubmed/26511587
http://dx.doi.org/10.1002/glia.22935
_version_ 1782430395228225536
author Martin, Heather L.
Santoro, Matteo
Mustafa, Sarah
Riedel, Gernot
Forrester, John V.
Teismann, Peter
author_facet Martin, Heather L.
Santoro, Matteo
Mustafa, Sarah
Riedel, Gernot
Forrester, John V.
Teismann, Peter
author_sort Martin, Heather L.
collection PubMed
description Parkinson's disease (PD) is the second most common neurodegenerative disease and results from the loss of dopaminergic neurons of the nigrostriatal pathway. The pathogenesis of PD is poorly understood, but inflammatory processes have been implicated. Indeed increases in the number of major histocompatibility complex II (MHC II) reactive cells have long been recognised in the brains of PD patients at post‐mortem. However whether cells expressing MHC II play an active role in PD pathogenesis has not been delineated. This was addressed utilising a transgenic mouse null for MHC II and the parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In wild‐type mice MHC II levels in the ventral midbrain were upregulated 1–2 days after MPTP treatment and MHC II was localized in both astrocytes and microglia. MHC II null mice showed significant reductions in MPTP‐induced dopaminergic neuron loss and a significantly reduced invasion of astrocytes and microglia in MHC II null mice receiving MPTP compared with controls. In addition, MHC II null mice failed to show increases in interferon‐γ or tumour necrosis factor‐α in the brain after MPTP treatment, as was found in wild‐type mice. However, interleukin‐1β was significantly increased in both wild‐type and MHC II null mice. These data indicate that in addition to microglial cell/myeloid cell activation MHC Class II‐mediated T cell activation is required for the full expression of pathology in this model of PD. GLIA 2016;64:386–395
format Online
Article
Text
id pubmed-4855685
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-48556852016-06-24 Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease Martin, Heather L. Santoro, Matteo Mustafa, Sarah Riedel, Gernot Forrester, John V. Teismann, Peter Glia Research Articles Parkinson's disease (PD) is the second most common neurodegenerative disease and results from the loss of dopaminergic neurons of the nigrostriatal pathway. The pathogenesis of PD is poorly understood, but inflammatory processes have been implicated. Indeed increases in the number of major histocompatibility complex II (MHC II) reactive cells have long been recognised in the brains of PD patients at post‐mortem. However whether cells expressing MHC II play an active role in PD pathogenesis has not been delineated. This was addressed utilising a transgenic mouse null for MHC II and the parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In wild‐type mice MHC II levels in the ventral midbrain were upregulated 1–2 days after MPTP treatment and MHC II was localized in both astrocytes and microglia. MHC II null mice showed significant reductions in MPTP‐induced dopaminergic neuron loss and a significantly reduced invasion of astrocytes and microglia in MHC II null mice receiving MPTP compared with controls. In addition, MHC II null mice failed to show increases in interferon‐γ or tumour necrosis factor‐α in the brain after MPTP treatment, as was found in wild‐type mice. However, interleukin‐1β was significantly increased in both wild‐type and MHC II null mice. These data indicate that in addition to microglial cell/myeloid cell activation MHC Class II‐mediated T cell activation is required for the full expression of pathology in this model of PD. GLIA 2016;64:386–395 John Wiley and Sons Inc. 2015-10-29 2016-03 /pmc/articles/PMC4855685/ /pubmed/26511587 http://dx.doi.org/10.1002/glia.22935 Text en © 2015 The Authors. Glia Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/3.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Martin, Heather L.
Santoro, Matteo
Mustafa, Sarah
Riedel, Gernot
Forrester, John V.
Teismann, Peter
Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease
title Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease
title_full Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease
title_fullStr Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease
title_full_unstemmed Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease
title_short Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease
title_sort evidence for a role of adaptive immune response in the disease pathogenesis of the mptp mouse model of parkinson's disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855685/
https://www.ncbi.nlm.nih.gov/pubmed/26511587
http://dx.doi.org/10.1002/glia.22935
work_keys_str_mv AT martinheatherl evidenceforaroleofadaptiveimmuneresponseinthediseasepathogenesisofthemptpmousemodelofparkinsonsdisease
AT santoromatteo evidenceforaroleofadaptiveimmuneresponseinthediseasepathogenesisofthemptpmousemodelofparkinsonsdisease
AT mustafasarah evidenceforaroleofadaptiveimmuneresponseinthediseasepathogenesisofthemptpmousemodelofparkinsonsdisease
AT riedelgernot evidenceforaroleofadaptiveimmuneresponseinthediseasepathogenesisofthemptpmousemodelofparkinsonsdisease
AT forresterjohnv evidenceforaroleofadaptiveimmuneresponseinthediseasepathogenesisofthemptpmousemodelofparkinsonsdisease
AT teismannpeter evidenceforaroleofadaptiveimmuneresponseinthediseasepathogenesisofthemptpmousemodelofparkinsonsdisease