Objective: To study disease progression in the transgenic (tg) hm2-α-SYN-39 mouse model of Parkinson´s disease (PD) by assessment of motor performance, dopaminergic neurodegeneration and T cell infiltration in the nigrostriatal tract.

Background: The adaptive immune system is believed to play a crucial role in the progression of PD. Autopsy findings in patients and studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated mice have shown an infiltration of CD4⁺ and CD8⁺ T cells into the substantia nigra (SN) and a neurotoxic effect of the CD4⁺ T cells. Since alteration of α-synuclein is crucial in PD pathogenesis, we here implemented the hm2-α-SYN-39 mouse model, which expresses the A30P and the A53T human α-synuclein mutations.

Method: The motor phenotype of tg and wildtype (wt) mice at 2-3 months (mo) and 16-17 mo of age was characterized via Rotarod performance test, open field and cylinder test. Dopaminergic neurodegeneration was analyzed by stereological quantification of tyrosine hydroxylase (TH)⁺ and Nissl⁺ neurons in the SN and by striatal TH stainings of terminals. CD4⁺ and CD8⁺ T cells in the SN and striatum were assessed immunohistochemically.

Results: At 2-3 mo of age, the Rotarod performance test revealed a significantly longer latency to fall in tg mice compared to wt mice, however, both groups showed a similar reduction in the latency to fall at age 16-17 mo. The open field and cylinder test showed no differences between tg and wt animals in locomotion or total rears, respectively, at 16-17 mo of age. Tg mice showed a loss of dopaminergic neurons in the SN with a significant reduction of 38% comparing 16-17 mo with 2-3 mo old mice (4228 ± 497.20 vs 6844 ± 535.70, p<0.01). A progressive low-grade infiltration of CD4⁺ and CD8⁺ T cells into the SN was observed in tg mice in contrast to wt control.

Conclusion: The hm2-α-SYN-39 mouse model shows no motor impairment with increasing age, but reveals a progressive dopaminergic neurodegeneration with infiltration of T cells into the SN. This is suggestive of a pathogenic involvement of the adaptive immune system in neurodegeneration in this PD mouse model that still needs to be further assessed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/disease-progression-characterized-by-motor-performance-dopaminergic-neurodegeneration-and-t-cell-infiltration-in-the-transgenic-hm2-%ce%b1-syn-39-mouse-model-of-parkinsons-disease/