Protective effects of 24-epibrassinolide against the 6-OHDA zebrafish model of Parkinson's disease
Ana Gomes, Sandra M. Monteiro, Carlos Venâncio, Luís Félix
Abstract
The molecular processes behind Parkinson's disease (PD) remain under debate although mitochondrial oxidative stress generation has been proposed as a fundamental contributor. In this context, different brassinosteroids have shown neuroprotective action hampering oxidative stress. This study determined the effects of 24-Epibrassinolide (24-EPI) against 6-hydroxydopamine- (6-OHDA-) induced toxicity using the zebrafish embryonic model. Embryos were exposed to 250 μM 6-OHDA or co-exposed to 24-EPI (0.01, 0.1, and 1 μM) for 3 days, starting at 48 h post-fertilization (hpf). During the experimental period, developmental parameters were assessed. At 120 hpf, larvae were tested for behavioural phenotypes with different biochemical biomarkers and tyrosine hydroxylase- (TH-) reactive neurons being also assessed. Exposure to 6-OHDA induced a decrease in body length while no other morphological phenotypes were noticed. A significant decrease in TH-neurons immunofluorescence, a decreased locomotion (speed and distance moved), and an increased absolute angle were found in 6-OHDA-exposed embryos. These outcomes were rescuable by the co-exposure with 24-EPI. Surprisingly, the direct effects of 6-OHDA on reactive oxygen species (ROS) were not observed in the present study supporting the involvement of other molecular pathways in the 6-OHDA-induced effects during embryonic development. Overall, the results obtained confirm PD-like symptoms induced by 6-OHDA during embryonic development which were reverted by 24-EPI. Although antioxidative signalling pathways deserve further scrutiny, the findings support the further investigation of 24-EPI neuroprotective effects.