Figure 6. Evidence for DAT-1 hyperactivation in tsp-17 worms.

A. dat-1::yfp transgenic worms (TG2470) do not exhibit hypersensitivity to 10 mM 6-OHDA. The extent of neurodegeneration was scored 72 h post 6-OHDA intoxication. Asterisks represent statistically significant differences compared to tsp-17 worms (****p<0.00001) B. More imipramine than in wild-type worms is needed to prevent neurodegeneration in tsp-17 mutants and in dat-1::yfp overexpression worms co-treated with 50 mM 6-OHDA. Data presented is from scoring the extent of neurodegeneration 72 h post 6-OHDA intoxication. The imipramine concentration is indicated on the x axis. N, total number of worms from each strain examined for every treatment. Error bars represent the standard error of the mean. Asterisks (below top bar) represent statistically significant differences compared to wild-type; worms treated with 0.125 mM imipramine are compared (****p<0.00001). Lower bars indicate difference within individual strains (no imipramine compared to 0.125 mM imipramine; *p<0.05, *p<0.005, ****p<0.00001) C., D. [³H]-dopamine (DA) uptake in wild-type and tsp-17 worms. Uptake assays were performed using 50 nM (C) and 250 nM [³H]-DA (D).