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...
Autores principales: | , , , , , |
---|---|
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 |