Mn toxicity in C.elegans

Manganese (Mn) is an essential ubiquitous transition metal and occupationally or environmentally overdosed a well-known risk factor for several neurological pathologies. However, the molecular mechanisms underlying Mn-induced neurotoxicity are largely unknown. In this study, utilizing the model organism Caenorhabditis elegans (C. elegans) for RNA-Seq analysis, as well as bioavailability and survival assays, key pathways of transcriptional response to Mn overexposure were investigated, providing an insight into the Mn-induced cellular stress and damage response. For this, worms were exposed to a subtoxic concentration of MnCl2 (100 mM) for different incubation durations. Comparative transcriptome analyses identified a large number of differentially expressed genes (DEGs) in nematodes exposed to MnCl2 and functional annotation suggests oxidative nucleotide damage, unfolded protein response, and innate immunity as major damage response pathways. Additionally, a distinct time-dependent increase of the transcriptional response after MnCl2 exposure was identified by means of increasing numbers of DEGs and GO terms, indicating a time-dependent response and activation of the stress response in Mn neurotoxicity. The here provided data represents a powerful transcriptomic resource in the field of Mn toxicity and therefore, this study provides a useful basis for further planning of targeted mechanistic studies of Mn-induced neurotoxicity that are desperately needed in the face of increasing industrial-caused environmental pollution with Mn.