Neurotoxic action of microcystin-LR is reflected in the transcriptional stress response of Caenorhabditis elegans

• The nematode C. elegans was exposed to the hepatotoxin microcystin-LR (MC-LR).
• MC-LR exposure leads to impairments in lifespan, reproduction and growth.
• A DNA-microarray revealed that neuromodulation was the dominant action.
• A miRNA-microarray showed that let-7 family-members were differentially regulated.
• In liver-lacking animals, neurotoxicity might be the primary effect of MC-LR.

Cyanobacterial blooms in aquatic environments are frequently characterized by elevated levels of microcystins, a potent hepatotoxin. Here we exposed the nematode Caenorhabditis elegans with environmentally realistic concentrations of MC-LR to explore its non-hepatic toxicity. Lifespan, reproduction and growth assays confirmed the toxic potential of 100 μg/L MC-LR even in this liver-lacking invertebrate. Whole-genome microarray analysis revealed that a neuromodulating action was the dominant response in nematodes challenged with 100 μg/L MC-LR. Indeed, most of the 201 differentially expressed genes were associated with neurobehavior, neurogenesis, and signaling associated pathways. In addition, a whole-genome miRNA-microarray highlighted that, in particular, members of the let-7 family were differentially regulated. These miRNAs are involved in the developmental timing of cell fates, including neurons, and are probably also part of the stress response system. To conclude, neurological modulation is the main transcriptional stress response in C. elegans exposed to MC-LR.