Abstract
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-g or tumour necrosis factor-a in the brain after MPTP treatment, as was found in wild-type mice. However, interleukin-1b was significantly increased in both wt 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.
Original language | English |
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Pages (from-to) | 386-395 |
Number of pages | 10 |
Journal | Glia |
Volume | 64 |
Issue number | 3 |
Early online date | 29 Oct 2015 |
DOIs | |
Publication status | Published - 1 Mar 2016 |
Bibliographical note
Funded byThe Parkinson's Disease Foundation
The Wellcome Trust (WT080782MF)
Biotechnology and Biological Sciences Research Council and the Royal Society
Acknowledgment
The authors are grateful to the staff of the Medical Research Facility for their help with the animal care. The authors have no conflicts of interest to declare.
Keywords
- microglia
- Parkinson's Disease
- MHCII
- MPTP
- neuroinflammation