Uric Acid Enhances Neurogenesis in a Parkinsonian Model by Remodeling Mitochondria
Abstract Adult neurogenesis is the process of generating new neurons to enter neural circuits and differentiate into functional neurons. However, it is significantly reduced in Parkinson’s disease (PD). Restoring neurogenesis is suggested to be a potential disease-modifying strategy to treat PD. Uric acid (UA), a natural antioxidant, has neuroprotective properties in patients with PD. Here, we hypothesized that UA would enhance neurogenesis by modulating mitochondria, dynamic organelles and key regulators of the fate of neural stem cells. We evaluated whether elevating serum UA levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian model would restore neurogenesis in the subventricular zone (SVZ). UA-elevating therapy significantly increased the number of bromodeoxyuridine (BrdU)-positive cells in the SVZ of PD animals as compared to PD mice with normal UA levels. In a cellular model, UA treatment promoted cell proliferation against 1-methyl-4-phenylpyridinium (MPP+) in primary cultured neural precursor cells (NPCs) from the SVZ. These findings demonstrate that UA enhances neurogenesis by modulating mitochondrial dynamics in the SVZ of parkinsonian models, suggesting UA elevating strategy as a potential disease-modifying therapy in treatment of parkinsonian disorders.
