The Role of De Novo Catecholamine Synthesis in Mediating Methylmercury-Induced Vesicular Dopamine Release From Rat Pheochromocytoma (PC12) Cells

Tiernan, Chelsea T.; Edwin, Ethan A.; Goudreau, John L.; Atchison, William D.; Lookingland, Keith J.

doi:10.1093/toxsci/kft025

Cited by 9 publications

(15 citation statements)

References 35 publications

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“…The concentration of dopamine at the synapse resulting from the cumulative activity of the aforementioned regulatory mechanisms, rather than overall tissue concentrations, ultimately influences the activity of dopaminergic neurons. Multiple studies have demonstrated increased presynaptic release of dopamine from brain tissue in rats, mice, and rat PC‐12 cell lines following MeHg exposure . In addition, the results of the present study show significant decreases in MAO activity in eggs incubated with MeHg concentrations as low as 0.048 ppm compared with controls (ANOVA, df = 5, F = 9.43, p < 0.01) .…”

Section: Resultssupporting

confidence: 65%

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

Bridges

Venables

Roberts

2016

Environmental Toxicology and Chemistry

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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.

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Section: Resultssupporting

confidence: 65%

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

Bridges

Venables

Roberts

2016

Environmental Toxicology and Chemistry

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“…MeHg has been reported to both facilitate and suppress exocytosis 17 34 35 . In addition, we recently reported that microglia release ATP by exocytosis via a vesicular nucleotide transporter (VNUT)-mediated pathway(s) 11 ; thus, we next investigated VNUT-mediated ATP release evoked by MeHg.…”

Section: Resultsmentioning

confidence: 99%

Microglia trigger astrocyte-mediated neuroprotection via purinergic gliotransmission

Shinozaki

Nomura

Iwatsuki

et al. 2014

Sci Rep

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Microglia are highly sensitive to even small changes in the brain environment, such as invasion of non-hazardous toxicants or the presymptomatic state of diseases. However, the physiological or pathophysiological consequences of their responses remain unknown. Here, we report that cultured microglia sense low concentrations of the neurotoxicant methylmercury (MeHglow) and provide neuroprotection against MeHg, for which astrocytes are also required. When exposed to MeHglow, microglia exocytosed ATP via p38 MAPK- and vesicular nucleotide transporter (VNUT)-dependent mechanisms. Astrocytes responded to the microglia-derived ATP via P2Y1 receptors and released interleukin-6 (IL-6), thereby protecting neurons against MeHglow. These neuroprotective actions were also observed in organotypic hippocampal slices from wild-type mice, but not in slices prepared from VNUT knockout or P2Y1 receptor knockout mice. These findings suggest that microglia sense and respond to even non-hazardous toxicants such as MeHglow and change their phenotype into a neuroprotective one, for which astrocytic support is required.

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“…MeHg-induced disruptions in choice co-occur with increased sensitivity to dopamine transporter (DAT) blockers, such as d -amphetamine (Rasmussen & Newland, 2001) and cocaine (Reed & Newland, 2009). Further, MeHg inhibits DAT (Dreiem, Shan, Okoniewski, Sanchez-Morrissey, & Seegal, 2009) and stimulates DA efflux both in vitro (Tiernan, Edwin, Goudreau, Atchison, & Lookingland, 2013) and in vivo (Faro, Do Nascimento, San José, Alfonso, & Durán, 2000). …”

mentioning

confidence: 99%

Effects of adolescent exposure to methylmercury and d-amphetamine on reversal learning and an extradimensional shift in male mice.

Boomhower¹,

Newland²

2017

Experimental and Clinical Psychopharmacology

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Adolescence is associated with the continued maturation of dopamine neurotransmission and is implicated in the etiology of many psychiatric illnesses. Adolescent exposure to neurotoxicants that distort dopamine neurotransmission, such as methylmercury (MeHg), may modify the effects of chronic d-amphetamine (d-AMP) administration on reversal learning and attentional-set shifting. Male C57Bl/6n mice were randomly assigned to two MeHg-exposure groups (0 ppm and 3 ppm) and two d-AMP-exposure groups (saline and 1 mg/kg/day), producing four treatment groups (n = 10–12/group): Control, MeHg, d-AMP, and MeHg + d-AMP. MeHg exposure (via drinking water) spanned postnatal day 21–59 (the murine adolescent period), and once daily i.p. injections of d-AMP or saline spanned postnatal day 28–42. As adults, mice were trained on a spatial-discrimination-reversal (SDR) task in which the spatial location of a lever press predicted reinforcement. Following two SDRs, a visual-discrimination task (extradimensional shift) was instated in which the presence of a stimulus light above a lever predicted reinforcement. Responding was modeled using a logistic function, which estimated the rate (slope) of a behavioral transition and trials required to complete half a transition (half-max). MeHg, d-AMP, and MeHg + d-AMP exposure increased estimates of half-max on the second reversal. MeHg exposure increased half-max and decreased the slope term following the extradimensional shift, but these effects did not occur following MeHg + d-AMP exposure. MeHg + d-AMP exposure produced more perseverative errors and omissions following a reversal. Adolescent exposure to MeHg can modify the behavioral effects of chronic d-AMP administration.

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The Role of De Novo Catecholamine Synthesis in Mediating Methylmercury-Induced Vesicular Dopamine Release From Rat Pheochromocytoma (PC12) Cells

Cited by 9 publications

References 35 publications

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

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

Microglia trigger astrocyte-mediated neuroprotection via purinergic gliotransmission

Effects of adolescent exposure to methylmercury and d-amphetamine on reversal learning and an extradimensional shift in male mice.

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