Meeting Abstract
29.6 Saturday, Jan. 4 14:45 Isolating the Impact on Voluntary Motor Control of Individual PD Pathologies and Potential Treatments in the Model Organism C. elegans BODUCH, C*; LIU, H; FIDELMA, O; St. Edward’s University, Austin cboduch@stedwards.edu
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons, diminished voluntary motor control, and aggregation of α-synuclein (AS) protein into Lewy bodies (Lundblad, 2002). The transgenic PD strains of C. elegans, NL5901 and CB1112, are useful models to examine progressive degeneration of locomotion over the organisms’ lifespan. NL5901 expresses human α-synuclein (AS); CB1112 is deficient in tyrosine hydroxylase, a biosynthetic enzyme in dopamine synthesis, thus mimicking the individual human PD pathologies. Additionally, RNAi knockdowns (KD) of HSP-90, confirmed to increase aggregations, were used to test the impact of AS aggregations on locomotive control. Both PD strains and KD were treated with dopamine agonist and dopamine reuptake inhibitor in order to strengthen dopaminergic signaling. Voluntary motor control for each group was examined daily for 9 days using a locomotive control index (LCI). The LCI data suggests the expression of AS alone significantly diminished locomotive control in C. elegans compared to N2 wt (t-test, p<0.001). The resulting increased AS aggregation in KD further decreased LCI compared to N2 (t-test, p<0.001). The data also shows a significant reduction of the LCI in CB1112 (dopamine-deficient) strain compared to N2 (t-test, p<0.001). Furthermore across all strains, motor deficits progressed with age; possibly due to a continuous increase in AS load, or to progressive degeneration of elements in the dopaminergic circuit. When strains were treated from birth to enhance dopaminergic signaling, the LCI rose for all strains. This suggests that strengthening the dopaminergic pathway was enough to partially restore locomotive control. Isolation of each of the pathologies of PD has provided insight into their individual impact on locomotive control in C. elegans.
