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

Heather L. Martin, Matteo Santoro, Sarah Mustafa, Gernot Riedel* (Corresponding Author), John V. Forrester, Peter Teismann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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 languageEnglish
Pages (from-to)386-395
Number of pages10
Issue number3
Early online date29 Oct 2015
Publication statusPublished - 1 Mar 2016


  • microglia
  • Parkinson's Disease
  • MPTP
  • neuroinflammation


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