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

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.

Toxicogenomics and Molecular Markers in Pollution

“…In addition to describing some of the outbreaks of mercury intoxication in human populations, this review also draws attention to the importance of furthering our understanding of the effects of low-dose exposure to the metal [ 6 ]. That is precisely what Glazer and Brennan [ 3 ] did in their study, finding that very low concentrations of methylmercury (as low as 5 nM) caused anxiety and an impaired stress response in both adults and developing animals. These symptoms have been previously detected in other models exposed to high doses of the metal, as well as other signs related to emotionality such as depression and insomnia [ 7 ].…”

“…The zebrafish model has also been used in the study by Glazer and Brennan [ 3 ] to analyze the deleterious consequences for early development of exposure to low doses of methylmercury, the most toxic form of mercury. The main target organ of methylmercury is the Central Nervous System (CNS) [ 4 , 5 ], and the mechanisms underlying the damage caused by the metal include oxidative stress, excitotoxicity, calcium imbalance, DNA damage, neuroinflammation, altered neurotransmission, impaired neurogenesis and cell death, as reviewed by Novo et al [ 6 ].…”

“…These symptoms have been previously detected in other models exposed to high doses of the metal, as well as other signs related to emotionality such as depression and insomnia [ 7 ]. However, the most interesting and novel result was the altered gene expression profile, which was associated with behavioral alterations, demonstrating the involvement of the dopaminergic system and the hypothalamic–pituitary–interrenal (HPI) axis in both stages of life (during development and in adulthood) exposed to low doses of MeHg [ 3 ]. This is important considering that all species of mercury can form deposits in the hypothalamus [ 7 ] and also because the HPI axis represents an example of the crosstalk between the brain and the periphery.…”