Fig. 2: Cytosolic accumulation of dopamine triggers a neuroprotective dopaminergic stress response.

a qPCR quantification of cat-2/TH in C. elegans (PMD216) raised on empty vector (EV) or cat-1/SLC18A2 RNAi. Unpaired two-tailed t-test. Mean ± SEM. n = 8 independent replicates. b qPCR quantification of cat-2/TH in C. elegans (PMD216) raised on EV, dop-2/DRD2, or 50/50 mixed cat-1/dop-2 RNAi. Ordinary one-way ANOVA with Šidák’s correction. Mean ± SEM. n = 5 independent replicates. c Dopaminergic GFP retention in worms (PMD216) 48 h after injury. Positive and negative values show enhanced and reduced GFP retention respectively compared to injured EV control. Unpaired two-tailed t-test. Mean ± 95% CI. From left to right, n = 3696 (EV), 3554 (cat-1) collected over 4 independent experiments. d Dopaminergic GFP retention in worms (PMD216) 48 h after injury, pretreated with 30 µM reserpine (Res) or vehicle (acetic acid). Positive and negative values show enhanced and reduced GFP retention respectively compared to injured vehicle. Unpaired two-tailed t-test. Mean ± 95%CI. From left to right, n = 1828 and 1757 collected over 3 independent experiments. e Cytosolic ROS production in dopaminergic neurons 48 h after injury (PMD185). 405 nm/488 nm oxidation ratio is normalized to uninjured, time-matched, and vehicle control (acetic acid). Reserpine (Res) was supplemented to pre-injury agar plates at a final concentration of 30 μM. Unpaired two-tailed t-test. Blue = injured and vehicle treated, beige = injured and reserpine pretreated. Mean ± 95%CI. From left to right, n = 485 and 552 collected over 3 independent experiments. f, g SYTOX green fluorescence in LUHMES cells after a 10 nM TG pulse, (ΔF/F0). Cells were pretreated with 1 µM reserpine prior to TG addition or treated with 10 µM reserpine after TG removal. AUC was used for statistical analysis with an unpaired two-tailed t-test. DD = days of differentiation, D post TG = days post TG treatment. Mean ± SEM. n = 2 independent replicates for (f) and n = 7-8 independent replicates for (f).