Figure 8.

Effects of 4 and 5 on 6-OHDA-induced neurodegeneration in C. elegans. Animals were treated with 4 or 5 (5 μM) in the presence of 6-OHDA (5 mM) for 30 min. At the end of incubation, treated animals were placed on fresh agar plates for 72 h and then visualized as described in the Materials and Methods section. (A) In nontreated vtIs7 [pdat-1::GFP] transgenic animals, dopaminergic neurons express GFP, with two of the four CEP cell bodies (white arrows) and relative dendrites (arrowheads) visible in this focal plane in the head. (B) 6-OHDA treatment causes the degeneration of CEP dendrites (empty arrowheads) and two cell bodies (gray arrows), in treated animals. The other two CEP neurons are not visible anymore. (C) Compound 5 cotreatment partially rescues the 6-OHDA-induced toxic effects, with degeneration of one of the CEP dendrites (empty arrowhead) but not the other (arrowhead) and with one CEP cell body still viable (white arrow) and one dying (gray arrow) in this focal plane. Pictures have been taken with epifluorescence microscopy; in all panels, the anterior part of the animal is on the left and ventral down. ADE neurons, which are less affected by 6-OHDA treatment, are also visible but were not scored (asterisks). (D) Quantification of degenerating CEP neurons. Data are expressed as percentages of degenerating neurons and reported as mean ± SEM of at least three independent experiments. The number of animals observed is n = 270, 130, and 272, respectively (** p < 0.01 versus animals treated with 6-OHDA at one-way ANOVA with the Kruskal–Wallis post hoc test).