Cerebroventricular Injection of Pgk1 Attenuates MPTP-Induced Neuronal Toxicity in Dopaminergic Cells in Zebrafish...

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons. While extracellular Pgk1 (ePgk1) is reported to promote neurite outgrowth, it remains unclear if it can affect the survival of dopaminergic cells. To address this, we employed cerebroventricular microinjection (CVMI) to deliver Pgk1 into the brain of larvae and adult zebrafish treated with methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a PD-like model. The number of dopamine-producing cells in ventral diencephalon clusters of Pgk1-injected, MPTP-treated embryos increased over that of MPTP-treated embryos. Swimming distances of Pgk1-injected, MPTP-treated larvae and adult zebrafish were much longer compared to MPTP-treated samples. The effect of injected Pgk1 on both dopamine-producing cells and locomotion was time- and dose-dependent. Indeed, injected Pgk1 could be detected, located on dopamine neurons. When the glycolytic mutant Pgk1, Pgk1-T378P, was injected into the brain of MPTP-treated zebrafish groups, the protective ability of dopaminergic neurons did not differ from that of normal Pgk1. Therefore, ePgk1 is functionally independent from intracellular Pgk1 serving as an energy supplier. Furthermore, when Pgk1 was added to the culture medium for culturing dopamine-like SH-SY5Y cells, it could reduce the ROS pathway and apoptosis caused by the neurotoxin MPP⁺. These results show that ePgk1 benefits the survival of dopamine-producing cells and decreases neurotoxin damage.