The Effect of glna Loss on the Physiological and Pathological Phenotype of Parkinson's Disease C. elegans.

Background: Parkinson's disease (PD) is a common neurodegenerative disease. Glutamate(Glu) excitotoxicity is one of the main pathogenesis of PD. Glutaminase (Gls) is an enzyme primarily responsible for catalyzing the hydrolysis and deamidation of glutamine (Gln) to produce Glu and ammonia. Inhibiting the function of Gls may have a beneficial effect on the treatment of PD by reducing the production of Glu. The homologous gene of Gls in C. elegans is glna.

Aims: To explore the effects of glna loss on physiological and pathological phenotype of PD C. elegans, and to provide new ideas and references for the research and treatment of PD.

Materials & methods: We used PD C. elegans UA44 and QIN27 to detect development and lifespan, behavior, degeneration of dopaminergic neurons, lipid levels, ROS levels, expression levels of common amino acids.

Results: Glna loss had no significant impact on the development and lifespan of PD C. elegans. Glna loss saved part of the decline of motor function, including the head thrash frequency and the body bend frequency, and the difference was significant. There was a trend of improvement in some motor behaviors, such as the ethanol avoidance experiment, while no improvement was observed in other experiments. Glna loss slowed down the degeneration of dopaminergic neurons. Glna loss increased the lipid levels and ROS levels in C. elegans. Glna loss decreased Glu content and increased Gln content in C. elegans.

Discussion: The effect of glna loss on PD C. elegans may be the result of multiple factors, such as the tissue types of α-syn expression in C. elegans, the PD C. elegans model used, the adverse effects of glna loss on other systems, and the changes in ROS levels in C. elegans. The specific mechanisms causing these phenomena are still unclear and need to be further explored.

Conclusion: Glna loss has a certain protective effect on dopaminergic neurons in PD C. elegans, while the improvement effect on movement and behavior is limited.