Comparative effects of mercury chloride and methylmercury exposure on early neurodevelopment in zebrafish larvae

Abstract

Mercury (Hg) is a ubiquitous environmental toxicant with important public health implications. Hg causes neurotoxicity through astrocytes, Ca 2+ , neurotransmitters, mitochondrial damage, elevations of reactive oxygen species and post-translational modifications. However, the similarities and differences between the neurotoxic mechanisms caused by different chemical forms of Hg remain unclear. Zebrafish embryos were exposed to methylmercury (MeHgCl) or mercury chloride (HgCl 2 ) (0, 4, 40, 400 nM) up for 96 h. HgCl 2 exposure could significantly decrease survival rate, body length and eye size, delay the hatching period, induce tail bending and reduce the locomotor activity, and these effects were aggravated in the MeHgCl group. The compounds could increase the number of apoptotic cells in the brain and downregulate the expression of Shha, Ngn1 and Nrd, which contribute to early nervous development. The underlying mechanisms were investigated by metabolomics data. Galactose metabolism, tyrosine metabolism and starch and sucrose metabolism pathways were disturbed after HgCl 2 or MeHgCl exposure. In addition, the levels of three neurotransmitters including tyrosine, dopamine and tryptophan were reduced after HgCl 2 or MeHgCl exposure. Oxidative stress is related to metabolite changes, such as changes in the putrescine, niacinamide and uric acid contents in the HgCl 2 group, and squalene in the MeHgCl group. These data indicated that downregulation of these genes and abnormal metabolic profile and pathways contribute to the neurotoxicity of HgCl 2 and MeHgCl.

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

“…In a recent study in zebrafish, the expressions of the two dopamine D2 receptors, drd2a and drd2b were compared between groups of bold and shy adult fish that were classified based on their response to the novel tank dive test [55], and it was found that both receptors were expressed at higher levels in the bold fish indicating their importance for stress-coping mechanisms. Furthermore, sensitivity of the developing DA system to MeHg exposure was previously shown in a wide range of experimental models including zebrafish, rodents and in vitro cell cultures [32,36,37,43,57,58]. Therefore, we proceeded to test the hypothesis that MeHg-induced changes to dopamine signalling during development, specifically the expression of the dopamine receptor drd2b, contributed to the combination of behavioural effects (i.e., increased stress response and locomotor impairment) observed in our study in larvae and adults.…”

“…In this study, the authors used transgenic zebrafish lines in which cells expressing the dat gene were fluorescently labelled. In a different study, dopamine levels were significantly decreased in MeHgexposed embryos [58], at a dose which also resulted in impaired larval locomotor activity. Furthermore, alteration of dopamine-mediated locomotor activity was associated with reduction in dopamine D2 receptor binding in infant (PND 14) and juvenile (PND 21) rats exposed to low doses of MeHg throughout the perinatal period [32,36], and developmental exposure to MeHg was shown to cause decreased response to amphetamine, a dopamineacting stimulant, in two-month old male mice [59].…”

Transcriptional Analyses of Acute Exposure to Methylmercury on Erythrocytes of Loggerhead Sea Turtle

“…In the comparison between Gc–Gs1 and Gs1–Gs5, we found that the pathways with the highest enrichment were the lysosome (four genes) and the Jak-STAT (three genes) pathways, pathways that participate in the regulation of the response to oxidative stress mediated by MeHg [ 62 , 63 ]. In the comparison between Gc–Gs1, Gs1–Gs5, and Gc–Gs5, genes that participate in sphingolipid metabolism, autophagy, apoptosis, the HIF signaling pathway, mTOR, and PI3K-Akt were also enriched, which have been reported to be upregulated or downregulated by MeHg [ 64 , 65 , 66 , 67 ] ( Figure 7 ).…”

Organ-Specific Metabolome Deciphering Cell Pathways to Cope with Mercury in Wild Fish (Golden Grey Mullet Chelon auratus)

“…Data suggested that environmentally relevant exposure scenarios might cause MeHg-mediated dysbiosis of the gut microbiome, contributing to neurotoxicity in fish. Recently, the effects of MeHg and iHg were investigated in zebrafish embryos [ 8 ]. The metabolism of galactose, starch, and sucrose was disturbed after exposure to both Hg forms, and the levels of the neurotransmitters tyrosine, dopamine, and tryptophan were reduced.…”