Developmental exposure of zebrafish to 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) elicits MPTP-like...

1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) is an endogenous metabolite of the industrial waste trichloroethylene (TCE) and has been implicated as a potent neurotoxicant in TCE-induced neurotoxicity. TaClo has been associated with Parkinson's disease (PD) due to its neurotoxic effects and structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Despite the similarities, limited studies have explored the comparative neurotoxicity of MPTP and TaClo within the same experimental models. Zebrafish (Danio rerio) are a powerful high throughput platform for neurotoxicology studies and have been used to evaluate TCE-associated developmental neurotoxicity; however, the role of TaClo in TCE-associated neurotoxicity in the zebrafish model is unknown. To address these gaps, we established an MPTP-induced PD zebrafish larval model and investigated the role of TaClo by comparing its neurotoxic effects with those of MPTP. We exposed embryonic zebrafish to TaClo (5, 50, or 500 ppb) or MPTP (0-17,325 ppb) for 5 consecutive days. We demonstrate that TaClo at 5 ppb elicits 303.2 ppb MPTP-like neurotoxicity in the developmental zebrafish. We determined the lethal concentration 50 of TaClo at the zebrafish larval model at 120 h post-fertilization was 7890 ppb. We show that embryonic zebrafish exposed to TaClo exhibit neurobehavioral impairments, diencephalic dopaminergic neuronal damage, increased cellular apoptosis, astrocytic loss, microgliosis, and altered glutathione peroxidase activity levels. These findings provide important insights into the neurotoxic mechanisms of TaClo and emphasize the utility of developmental zebrafish as a model for studying TaClo-induced neurotoxicity. Our work contributes to environmental contaminants research in neurodegenerative diseases by providing evidence of the potential link between TaClo exposure and PD.