Figure 1. Pharmacological acetylcholinesterase inhibition ameliorates mutant ATXN3-medited motor defects in a SCA3 C elegans model:A: neostigmine (0.01-10.0 mM) shows no major toxic effects in C. elegans. Toxicity was assessed using the food clearance assay. The optical density of the OP50 suspension with neostigmne-treated animals (N2) at the concentrations depicted, was measured daily. The mean OD was calculated for each day from five samples and plotted over time. Control DMSO (1%) corresponds to drug vehicle and DMSO at 5% was used as positive (toxic compound) control. B: Locomotion defective behaviour of AT3q130 animals, comparison between treated (neostigmine 0.01-10 mM) and untreated animals in comparison to wild type (N2) and AT3q14 controls. Statistical significant difference determined using One-way ANOVA and Bonferroni's multiple comparison analysis compared to AT3q130 control: ***p≤0.001 (decreased motility); *p≤0.05, ***p≤0.001; n=5 C: Locomotion defective behaviour of AT3q130 animals, comparison between treated (neostigmine 0.1-10 µM) and untreated animals in comparison to wild type (N2) and AT3q14 controls. Statistical significant difference determined using One-way ANOVA and Bonferroni's multiple comparison analysis compared to AT3q130 control: ***p≤0.001, **p≤0.01, n=5 D: Locomotion defective behaviour of AT3q130 animals compared to double mutant AT3q130;
ace-1 and WT and
ace-1 control. Statistical significant difference determined using One-way ANOVA and Bonferroni's multiple comparison analysis: ***p≤0.001, ns-not significant; n=5 E: Locomotion defective behaviour of AT3q130 animals compared to double mutant AT3q130;
ace-2 and WT and
ace-2 control. Statistical significant difference determined using One-way ANOVA and Bonferroni's multiple comparison analysis: *p≤0.05, **p≤0.01, ns-not significant; n=4