Developmental Exposure to Low Concentrations of Methylmercury Causes Increase in Anxiety-Related Behaviour and Locomotor Impairments in Zebrafish

Int J Mol Sci. 2021 Oct 11;22(20):10961. doi: 10.3390/ijms222010961.

Abstract

Methylmercury (MeHg) is a ubiquitous pollutant shown to cause developmental neurotoxicity, even at low levels. However, there is still a large gap in our understanding of the mechanisms linking early-life exposure to life-long behavioural impairments. Our aim was to characterise the short- and long-term effects of developmental exposure to low doses of MeHg on anxiety-related behaviours in zebrafish, and to test the involvement of neurological pathways related to stress-response. Zebrafish embryos were exposed to sub-acute doses of MeHg (0, 5, 10, 15, 30 nM) throughout embryo-development, and tested for anxiety-related behaviours and locomotor activity at larval (light/dark locomotor activity) and adult (novel tank and tap assays) life-stages. Exposure to all doses of MeHg caused increased anxiety-related responses; heightened response to the transition from light to dark in larvae, and a stronger dive response in adults. In addition, impairment in locomotor activity was observed in the higher doses in both larvae and adults. Finally, the expressions of several neural stress-response genes from the HPI-axis and dopaminergic system were found to be disrupted in both life-stages. Our results provide important insights into dose-dependent differences in exposure outcomes, the development of delayed effects over the life-time of exposed individuals and the potential mechanisms underlying these effects.

Keywords: HPI-axis; anxiety; behaviour; developmental neurotoxicity; dopaminergic system; locomotor activity; methylmercury; zebrafish.

MeSH terms

  • Animals
  • Anxiety / etiology
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Embryo, Nonmammalian / drug effects
  • Embryonic Development / drug effects
  • Gene Expression / drug effects
  • Larva / drug effects
  • Larva / physiology
  • Locomotion / drug effects*
  • Methylmercury Compounds / toxicity*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Zebrafish / growth & development
  • Zebrafish / physiology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Methylmercury Compounds
  • Receptors, Dopamine D2
  • Zebrafish Proteins