Neurotoxicological evaluation of microcystin-LR exposure at environmental relevant concentrations on nematode...

Previous studies have not examined the adverse effects of microcystin-LR (MC-LR) at environmental relevant concentrations on the development and functions of nervous system. The neurotoxic effects of MC-LR exposure on neurotransmitter systems were investigated in Caenorhabditis elegans. After exposing L1 larvae to 0.1, 1, 10, and 100 μg l(-1) of MC-LR for 8 and 24 h, the adverse effects on GABAergic, cholinergic, serotonergic, dopaminergic, and glutamatergic neurons were examined. The expression levels of genes required for development and functions of GABAergic neurons were further investigated. Body bend frequency and head thrash frequency decreased significantly after MC-LR exposure for 8 h at concentrations more than 1 μg l(-1) and after MC-LR exposure for 24 h at concentrations more than 0.1 μg l(-1). Loss of GABAergic neurons increased significantly in a dose-dependent manner after MC-LR exposure at concentrations more than 0.1 μg l(-1). In contrast, no obvious neuronal losses or morphologic changes were observed in cholinergic, serotonergic, dopaminergic, and glutamatergic neurons in MC-LR-exposed nematodes. Quantitative real-time PCR assay further showed that expression levels of unc-30, unc-46, unc-47, and exp-1 genes required for development and function of GABAergic neurons decreased significantly in nematodes exposed to MC-LR at concentrations more than 0.1 or 1 μg l(-1). MC-LR at environmental relevant concentrations caused neurobehavioral defects, which may be largely due to the neuronal loss and the alterations of expression level of genes required for GABAergic neurotransmitter system in C. elegans.