Platelet factor 4 ameliorates motor and mood deficits in Parkinson’s disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms(1). Platelet factor 4 (PF4) is a platelets-secreted chemokine that can be activated by physical exercise. Recent studies showed that PF4 could improve cognition in aged mice(2), though whether it influences other neurological functions is vague. Here we investigated the role of PF4 in PD and normal aging mice. Intravenous administration of exogenous PF4 ameliorated both motor and non-motor symptoms of MPTP-induced PD mice, accompanying with reduced loss of nigrostriatal dopaminergic neurons and attenuated neuroinflammation in these regions. RNA sequencing showed that pathways related to inflammation were suppressed by PF4, which were confirmed by qPCR and immunohistochemical analysis. More interestingly, PF4 can also ameliorate the motor and non-motor symptoms after the loss of nigrostriatal dopaminergic neurons, and the efficacy can last for 3 weeks after PF4 administration. In addition, an improvement of motor performance and mood by PF4 was also observed in aged but not young mice. Collectively, our results show the potential of PF4 that not only be a therapeutic candidate for PD patients, but also be an option for aged people to improve their neurological performance. We investigated the role of PF4 in MPTP-induced PD mice. MPTP was injected intraperitoneally for 7 days. PF4 was injected intravenously every 3 days encompassing the whole experiment. The midbrains of 3 C57BL/6 mice from each group were used for RNA sequencing.