Dual Roles of Microglia in the Basal Ganglia in Parkinson's Disease.

With the increasing age of the population, the incidence of Parkinson's disease (PD) has increased exponentially. The development of novel therapeutic interventions requires an understanding of the involvement of senescent brain cells in the pathogenesis of PD. In this review, we highlight the roles played by microglia in the basal ganglia in the pathophysiological processes of PD. In PD, dopaminergic (DAergic) neuronal degeneration in the substantia nigra pars compacta (SNc) activates the microglia, which then promote DAergic neuronal degeneration by releasing potentially neurotoxic factors, including nitric oxide, cytokines, and reactive oxygen species. On the other hand, microglia are also activated in the basal ganglia outputs (the substantia nigra pars reticulata and the globus pallidus) in response to excess glutamate released from hyperactive subthalamic nuclei-derived synapses. The activated microglia then eliminate the hyperactive glutamatergic synapses. Synapse elimination may be the mechanism underlying the compensation that masks the appearance of PD symptoms despite substantial DAergic neuronal loss. Microglial senescence may correlate with their enhanced neurotoxicity in the SNc and the reduced compensatory actions in the basal ganglia outputs. The dual roles of microglia in different basal ganglia regions make it difficult to develop interventions targeting microglia for PD treatment.