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

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‐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

TracMouse: A computer aided movement analysis script for the mouse inverted horizontal grid test

“…Only a small cohort of mice was tested for feasibility and sensitivity of method, but more routine studies will follow in the future. Clearly, our histopathological analysis confirmed the significant lowering of striatal dopamine and loss of substantia nigra neurons as pertinent for Parkinsonian models242526. This resulted in a heightened number and distance covered by forepaw movements relative to controls.…”

Type‐1 interferons contribute to the neuroinflammatory response and disease progression of the MPTP mouse model of Parkinson's disease

“…The infiltration of CD41 and CD81 T cells in the PD brain has been demonstrated (Brochard et al, 2009). In addition, MHC II null mice display attenuated microgliosis and astrogliosis with reduced MPTP-induced DA cell loss supporting a role for the adaptive immune response in the disease progression (Martin et al, 2016). Therefore the influence of the type-1 IFNs on the peripheral immune response in Parkinson's disease warrants further study.…”

Effect of dental pulp stem cells in MPTP‐induced old‐aged mice model

“…Therefore, activated microglia may play a key role in neuro-inflammatory processes contributing to the pathogenesis of PD [39]. For instance, increased expression of ILs, IFN signalling and major histocompatibility complex II (MHC II) reactive cells in both postmortem human PD samples and in the MPTP mouse model indicated their involvement in activating neuro-inflammatory responses and disease progression [40,41]. Likewise, the elevation of anti-inflammatory mediators such as IL13, IL4, IL10 and TNF-a after the administration of DPSCs revealed the regulation of microglia activation/de-activation as the underlying mechanism of this phenomena.…”