Effects of dietary methylmercury on the dopaminergic system of adult fathead minnows and their offspring

Abstract

Mercury (Hg) is a ubiquitous environmental contaminant and potent neurotoxin, which may be transformed by bacteria in aquatic ecosystems to methylmercury (MeHg), an organic form which bioaccumulates and biomagnifies. Consequently, long-lived organisms at the top of the food web are at risk of dietary MeHg exposure, which can be actively transferred from mother to offspring. Exposure during neurodevelopment can lead to serious, irreversible neurological dysfunction, associated with a variety of cognitive and motor abnormalities. At low dietary concentrations, MeHg exposure has been associated with deficits in attention and hyperactivity in multiple species. Pathways associated with cognitive function and motor activity are primarily associated with the dopaminergic system. The present study used a model fish species, Pimephales promelas, to examine the effects of MeHg exposure on dopamine concentrations and monoamine oxidase activity in embryos and adult brains. Adult fatheads were exposed for 30 d to either a control or a treated diet (0.72 ppm Hg). Embryonic and larval exposures were a result of maternal transfer of dietary MeHg. The authors confirmed hyperactive behaviors in embryos and detected significant changes in embryonic dopamine concentrations. Similar effects on dopamine concentrations were seen in the telencephalon of adult brains. Exposure to MeHg also corresponded with a significant decrease in monoamine oxidase activity in both embryos and brain tissue. Collectively, these results suggest that current exposure scenarios in North America are sufficient to induce alterations to this highly conserved neurochemical pathway in offspring, which may have adverse effects on fish behavior and cognition. Environ Toxicol Chem 2017;36:1077-1084. © 2016 SETAC.

Effects of 2,4,6-Trichlorophenol on Clarias batrachus: a biomarkers approach

“…2,4,6-TCP might likely have inhibited GH secretion by acting at the level of hypothalamo-hypophysial axis. Moreover, brain amines also exert a control on the release of GH (Canosa et al 2007 ), and toxicants affect the secretion of monoamine oxidase (Bridges et al 2017 ). Thus, 2,4,6-TCP probably acts at the HPG level to inhibit GH secretion.…”

Alterations to the Intestinal Microbiome and Metabolome ofPimephales promelasandMus musculusFollowing Exposure to Dietary Methylmercury

“…We previously published companion studies showing a range of developmental effects in ELS fathead minnows (FHM) exposed to maternally transferred MeHg. Results showed WW egg Hg concentrations at the lower end of the reported range of concentrations (low treatment mean: 0.04–0.06 μg/g Hg) were sufficient to induce neurological effects. , …”

“…Numerous studies exist, which link exposure to metals to neurodegenerative diseases in vertebrates. − Parkinson’s disease (PD) is characterized by dopaminergic neuron loss in the midbrain from mitochondria-initiated oxidative stress, leading to changes in motor activity. − Similarly, MeHg has also been shown to preferentially accumulate in the mitochondria of neurons within the CNS, leading to a cascade of biochemical changes which culminate in oxidative stress, neuronal degeneration, and altered neurotransmission. ,,,,, Changes in motor activity were observed in embryonic FHM following developmental exposure to maternally transferred MeHg. , Though studies on neurodegeneration have typically focused on the CNS, there is an emerging link between nervous system function and gut microbiota . Interestingly, intestinal microbes produce almost half of the body’s dopamine (DA) from dietary substrates, forming the basis for bidirectional communication between intestinal microbes and the CNS. , This relationship is known as the microbiome–gut–brain axis implying a role for enteric microbiota in brain function and neurodevelopment. ,, Recently, a link between altered gut microbiome and Parkinson’s disease (PD) has been established in humans.…”

“…This effect on DA was also seen in the offspring of these animals along with motor-activity abnormalities, both hallmarks of dopaminergic neuron degeneration. , Another goal of this study was to add to the growing body of evidence suggesting small-bodied teleosts and their offspring may serve as surrogates for higher-vertebrate model species typically used to study neurodegenerative diseases in humans. To that end, we replicated the experiment using male CD-1 mice ( Mus musculus ) and performed metabolomics on the midbrains and gut microbiome analyses of sacrificed animals to compare with fish data . Finally, to further investigate mechanisms driving neurodevelopmental toxicity of MeHg, we performed metabolomics on newly hatched larvae to screen for changes in a range of low molecular weight metabolites and used the data to generate hypotheses regarding genes that may be differentially expressed.…”

The neurological toxicity of heavy metals: A fish perspective

“…In adults, these studies have shown that at levels less than 200 ppb, MeHg inhibits membrane adenosine deaminase, and results in mt2 gene induction in the brain but otherwise has minimal impact on other brain transcripts 79–81 . Mid-range levels (between 720 to 5500 ppb) show significant Hg accumulation in the brain 82 , delayed hatching, and increased mortality 83 , and the induction of hyperactive behavior coupled with decreased levels of the neurotransmitters, serotonin and dopamine 84,85 . At high doses (10 – 13 ppm), studies show alterations in proteins associated with gap junctions and oxidative phosphorylation, large increases in mt2, and mitochondrial dysfunction 81,82,86 .…”