Specialized pro-resolving mediator RvD1 reduces neuroinflammation in a transgenic rat model of Parkinson’s disease

The neuroinflammatory processes in Parkinson’s disease (PD) are usually associated with activation of the immune system caused by a growing aggregation of α-synuclein (α-Syn) in central nervous system. The active immune response in brain of PD patients leads to infiltration of lymphocytes, production of cytokines and microgliosis, these features could be a consequence of failure to resolve inflammation, a process mediated by a superfamily of endogenous lipids termed specialized pro-resolvin mediators (SPMs). A previous study from our group has shown that precocious treatment with resolvin D1 (RvD1) prevents the onset of PD by attenuating immune response in a rat model of PD. Herein, we explored the long-term effect of RvD1 in α-Syn rats by treating them with intraperitoneal injections twice a week, starting at early stage of the disease (2 months old) until the symptomatic phase (12 months old). Hence, we assessed motor deficit evaluated through Rotarod test and the infiltration of the main CD45+ leukocyte cell populations (i.e. CD3+ T-cells, CD45RA+ B-cells, CD161+ NK-cells and CD45/CD11bhigh macrophages) within substantia nigra and striatum by flow cytometry. We found that α-Syn rats showed a higher degree of nigral and striatal infiltration of all cell subsets compared to age-matched wildtype rats and that RvD1 treatment not only ameliorated motor deficits but also reduced their infiltration in both anatomical regions. Furthermore, although the percentage of CD45lowCD11b+ microglial cells remained unchanged between the different experimental groups, we observed that microglia of α-Syn rats shifted from a pro-inflammatory M1-like to a pro-resolving/anti-inflammatory M2-like immunophenotype upon RvD1 treatment, in terms of modulation of their respective M1 (CD68, CD86, MHC-II) and M2 (CD206, TREM2) markers. These results suggest that RvD1 is able to delay disease progression by blunting neuroinflammation and inducing a microglia- driven pro-resolving response