Effects of Methylcyclopentadienyl Manganese Trycarbonil on dopaminergic neurons in zebrafsh

Heavy metals are environmental factors whose role in the pathogenesis of several neurological disorders is taken increasingly into account. Alteration of brain manganese (Mn) homeostasis has been linked to neurodegenerative diseases, such as Alzheimer and Parkinson’s. Strong concern was expressed over Methylcyclopentadienyl Manganese Trycarbonil (MMT), an organic Mn-containing gasoline additive, due to health risk from long-term exposure. Despite evidence of structural and functional damage induced by Mn-based chemicals on dopaminergic (DA) neurons, no in vivo studies on neuronal differentiation have been performed. This study aims to investigate transcriptional, morphological and behavioral alterations caused by sub-lethal (30–100 µM) MMT exposure during neuronal differentiation in zebrafish. Zebrafish is a useful model organism for studying effects of neurotoxicants on the nervous system, by virtue of teleost brain homologies with the mammalian one. Zebrafish embryos exposed to MMT at critical developmental stages of DA differentiation showed transcriptional alteration of genes involved in specification, intermediate differentiation and maturation of DA neurons. MMT treatment was also able to alter morphology, number and size of specific clusters of DA neurons. MMT treatment evoked a hyperactive behavior in embryos. Embryos treated with MMT were grown up to 5 months and submitted to the Y-maze test for evaluating their behavior. The analysis revealed changes in cognitive capabilities affecting exploration, orientation and spatial memory. Collectively, these findings suggest that chronic exposure to sub-lethal MMT during neuronal differentiation can alter the development of DA neurons and the short- and long-term behavioural traits controlled by the DA system.