Microcystin-LR-Triggered Neuronal Toxicity in Whitefish Does Not Involve MiR124-3p

Neurotox Res. 2019 Jan;35(1):29-40. doi: 10.1007/s12640-018-9920-4. Epub 2018 Jun 7.

Abstract

Microcystin-LR (MC-LR) is a potent hepatotoxin that has also been pointed out of causing neurotoxicity, but the exact mechanisms of action still remain ambiguous and need to be elucidated. Data from studies on mammals show that pathology of astrocyte cells points to perturbations of microRNA signaling. Glial fibrillary acidic protein (GFAP), a neuronal cell/astrocyte-specific protein, and a microRNA-124-3p (MiR124-3p) are among putative triggers and regulators of neuronal cell/astrocyte reactivity. In the present study on whitefish (Coregonus lavaretus), we found that gfap mRNA contains a putative target site for MIR124-3p, to potentially affect its expression changes. qPCR expression study of gfap:MiR124-3p pair in the midbrain of juvenile whitefish, during 28 days of exposure to a repeated subacute dose of MC-LR (100 μg kg-1 body mass), showed marginally significant up-regulation of gfap only on the 7th day of exposure period which suggests neuronal toxicity. During the whole exposure period, neither midbrain nor blood plasma levels of MiR124-3p were changed. Furthermore, double luciferase gene reporter assay confirmed the lack of MiR124-3p involvement in mediating control over gfap mRNA expression. These data show that, although MC-LR may trigger neuronal toxicity in whitefish, this does not involve MiR124-3p in response to the treatment.

Keywords: Circulating microRNA; Gliosis; Neurotoxicity; microRNA.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Enzyme Inhibitors / toxicity*
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • HEK293 Cells
  • Humans
  • Marine Toxins
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Microcystins / toxicity*
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Phylogeny
  • Salmonidae
  • Transfection
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • Enzyme Inhibitors
  • Glial Fibrillary Acidic Protein
  • MIRN1243 microRNA, human
  • Marine Toxins
  • MicroRNAs
  • Microcystins
  • cyanoginosin LR