Resynchronization of microglial activity in the brain is associated with restoration of motor function in Parkinson’s disease

Neuroinflammation is a key factor in Parkinson's disease (PD) pathogenesis. However, the regional heterogeneity of biomarkers related to inflammation in PD is less well defined. We developed [18F]GSK PET imaging to quantify neuroinflammation via the P2X7 receptor (P2X7R) in A53T PD male mice and wild-type (WT) male mice. Montelukast (MK) was administered to mice, and weekly behavior tests confirmed MK's efficacy. [18F]L-DOPA/[18F]GSK PET, motor testing, autoradiography, and immunofluorescence were performed after MK treatments. MK improved motor function and reduced the brain uptake of [18F]GSK, indicating resynchronization of regional microglial activity. The whole brain uptake of [18F]GSK was correlated with motor functional restoration, while [18F]L-DOPA PET was not. Overall, our study indicated that brain mapping of [18F]GSK PET is beneficial for exploring P2X7R-related neuroinflammation, which is correspondent to motor function in PD. Brain PET-MRI imaging shows higher [18F]GSK uptake across multiple regions in A53T compared to WT mice. Correlation analyses reveal that resynchronization of microglia in Parkinson's disease is associated with motor function restoration.