Effects of dietary methylmercury on the zebrafish brain: histological, mitochondrial, and gene transcription analyses

Abstract

The neurotoxic compound methylmercury (MeHg) is a commonly encountered pollutant in the environment, and constitutes a hazard for wildlife and human health through fish consumption. To study the neurotoxic impact of MeHg on piscivorous fish, we contaminated the model fish species Danio rerio for 25 and 50 days with food containing 13.5 μg/g dry weight (dw) of MeHg (0.6 μg MeHg/fish/day), an environmentally relevant dose leading to brain mercury concentrations of 30 ± 4 μg of Hg g(-1) (dw) after 25 days of exposure and 46 ± 7 μg of Hg g(-1) (dw) after 50 days. Brain mitochondrial respiration was not modified by exposure to MeHg, contrary to what happens in skeletal muscles. A 6-fold increase in the expression of the sdh gene encoding the succinate dehydrogenase Fe/S protein subunit was detected in the contaminated brain after 50 days of exposure. An up regulation of 3 genes, atp2b3a, atp2b3b, and slc8a2b, encoding for calcium transporters was noticed after 25 days of exposure but the atp2b3a and atp2b3b were repressed and the slc8a2b gene expression returned to its basal level after 50 days, suggesting a perturbation of calcium homeostasis. After 50 days, we detected the up regulation of glial fibrillary acidic protein and glutathione S-transferase genes (gfap and gst), along with a repression of the glutathione peroxidase gene gpx1. These results match well with a MeHg-induced onset of oxidative stress and inflammation. A transmission electron microscopic observation confirmed an impairment of the optical tectum integrity, with a decrease of the nucleal area in contaminated granular cells compared to control cells, and a lower density of cells in the contaminated tissue. A potential functional significance of such changes observed in optical tectum when considering wild fish contaminated in their natural habitat might be an impaired vision and therefore a lowered adaptability to their environment.

Novel biomarkers of mercury-induced autoimmune dysfunction: A cross-sectional study in Amazonian Brazil

“…Others have shown that polymorphisms in GSTA1 genes confer protection against immune activation by exposure to xenobiotics in vulcanization processes (Jonsson et al 2008), presumable because these polymorphisms reduce the enzyme inhibition induced by xenobiotic compound binding to the enzyme (El-Demerdash 2001). While heavy metal exposure and binding may decrease glutathione transferase (but not GSTA) enzymatic activity, exposure to mercury has been shown to increase expression of glutathione transferase mRNAs (Cambier et al 2012; Korashy and El-Kadi 2006) in cell culture and zebrafish model systems. However, these studies examined expression of the gene transcript or the protein itself rather than the development of autoantibodies reactive with the protein as we have reported here.…”

Differential gene expression associated with dietary methylmercury (MeHg) exposure in rainbow trout (Oncorhynchus mykiss) and zebrafish (Danio rerio)

“…MeHg can cross the blood-brain barrier and accumulate to a significant degree in the brain and induce neurotoxicity (Kerper et al 1992; Berntssen et al 2003; Gonzalez et al 2005). Research in rainbow trout (Giblin et al 1973) and zebrafish (Cambier et al 2010, 2012) shows that MeHg can accumulate in lens, brain, skeletal muscle, blood and spleen. Recent research in spotted dogfish ( Scyliorhinus canicula ) shows that the bioaccumulation of mercury followed the order muscle > heart > liver > gills > pancreas (Coelho et al 2010).…”

Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity

“…Quantitative PCR (qPCR) can be used to evaluate alterations in gene expression [198]; however, the information is limited to the number of genes investigated.…”

“…Methylmercury is associated with Minamata disease and nervous system impairment. Cambier et al [198] fed adult male fish food contaminated with methylmercury and found changes in gene expression in the GABA synthesis and metabolism pathways. Inorganic mercury is associated with acute toxicity and renal failure; however, Richetti et al [262] found that adult zebrafish exposed to mercury chloride and lead acetate had decreased activity of acetylcholinesterase, but no alterations in the gene expression of AChE.…”