Manganese-Induced Toxicity in C. elegans: What Can We Learn from the Transcriptome?

Merle M. Nicolai, Marcello Pirritano, Gilles Gasparoni, Michael Aschner, Martin Simon, Julia Bornhorst

Research output: Contribution to journalArticlepeer-review

Abstract

Manganese (Mn) is an essential ubiquitous transition metal and, when occupationally or environmentally overexposed, a well-known risk factor for several neurological pathologies. However, the molecular mechanisms underlying Mn-induced neurotoxicity are largely unknown. In this study, addressing RNA-Seq analysis, bioavailability and survival assays, key pathways of transcriptional responses to Mn overexposure were investigated in the model organism Caenorhabditis elegans (C. elegans), providing insights into the Mn-induced cellular stress and damage response. Comparative transcriptome analyses identified a large number of differentially expressed genes (DEGs) in nematodes exposed to MnCl2, and functional annotation suggested oxidative nucleotide damage, unfolded protein response and innate immunity as major damage response pathways. Additionally, a time-dependent increase in the transcriptional response after MnCl2 exposure was identified by means of increased numbers of DEGs, indicating a time-dependent response and activation of the stress responses in Mn neurotoxicity. The data provided here represent 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 urgently needed in the face of increasing industrially caused environmental pollution with Mn.

Original languageEnglish (US)
Article number10748
JournalInternational Journal of Molecular Sciences
Volume23
Issue number18
DOIs
StatePublished - Sep 2022

Keywords

  • Caenorhabditis elegans
  • manganese
  • metal response
  • oxidative stress
  • stress response
  • transcriptome analysis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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