Meeting Abstract
29.5 Saturday, Jan. 4 14:30 Investigating the Effect of Dopamine Deficiency, its Impact on Octopamine Signaling, as well as Treatments in a C. elegans Model of Parkinson’s Disease CAPUTO, C.R.; St. Edward’s University ccaputo2@stedwards.edu
Investigating the Effect of Dopamine Deficiency, its Impact on Octopamine Signaling, as well as Treatments in a C. elegans Model of Parkinson’s Disease. Parkinson’s disease (PD) is a progressive neurodegenerative disease which affects roughly 500,000 United States citizens, with 50,000 new cases diagnosed each year. Clinically, PD expresses itself in a variety of neuromuscular and cognitive forms. It is important to better understand the molecular and physiological nature of conventional treatment methods. The purpose of this study was threefold; to determine the effects of a complete loss of dopaminergic (DA) neurotransmitters in Caenorhabditis elegans, to evaluate potential disruptions in the octopamine/dopamine synthesis pathways as a result, and to try and mitigate any effects of DA deficiency. The drugs used in this experiment were the DA agonist quinpirole and the dopamine reuptake-inhibitor nomifensine. We used a transgenic strain of C. elegans with tyrosine hydroxylase, a DA biosynthetic enzyme, knocked out, wildtype N2, and the DA deficient strain. Worms were exposed to quinpirole-via their E. coli food source. They were subsequently tested throughout their lives with multiple assays compared to N2. We found that quinpirole does rescue problems stemming from the lack of DA, and it improved the PD strain’s thrashing ability by 69% at day 12. It was also found that octopamine levels are raised in DA deficient worms, as a more than 200% increase in movement was found when looking at foraging behaviors comparing N2 to PD strain. The octopamine increase was found to be partially reversed when using quinpirole along with the DA reuptake inhibitor nomifensine. This finding, along with the ability of the DA agonist alone to rescue physiological and behavioral deficits, provides insights into potential treatments.
