Effect of methylmercury on brain acetylcholine concentration and turnover in mice

Kobayashi, Haruo; Yuyama, Akira; Matsusaka, Naonori; Takeno, Kazu; Yanagiya, Iwao

doi:10.1016/0041-008x(80)90002-2

Cited by 25 publications

(7 citation statements)

References 38 publications

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“…In vitro, MeHg can inhibit the activity of ChAT (i.e., decreased synthesis of ACh; Dwivedi et al, 1980;Kobayashi et al, 1979;Omata et al, 1982), ligand binding to the mACh receptor (i.e., reduced signal transduction; Abd-Elfattah and Shamoo, 1981; Basu et al, 2005c), and reuptake of choline (i.e., reduced ACh turnover; Kobayashi et al, 1979). These results are supported in vivo, as MeHg can reduce ChAT activity (Dwivedi et al, 1980;Omata et al, 1982) and ACh content (Hrdina et al, 1976;Kobayashi et al, 1980). Despite these data, we did not measure any changes in ChAT activity, ACh concentration, or levels of choline transporter.…”

Section: Discussionmentioning

confidence: 93%

“…Studies in wild (Basu et al, 2005a,b, under review) and laboratory (Coccini et al, 2000;Dwivedi et al, 1980;Hrdina et al, 1976;Kobayashi et al, 1980;Omata et al, 1982) animals have shown that MeHg can alter components of the cholinergic system. The effects on this system are nonspecific and are caused by the interactions of MeHg with sulfhydrylcontaining proteins, which are ubiquitous in all cells.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, MeHg can inhibit the neuronal uptake of choline (Kobayashi et al, 1979), activity of choline acetyltransferase (ChAT) (Dwivedi et al, 1980;Kobayashi et al, 1979;Omata et al, 1982), and binding to the muscarinic acetylcholine (mACh) receptor (Abd-Elfattah and Shamoo, 1981;Basu et al, 2005c). In vivo, exposure to MeHg has been linked with decreased activity of ChAT (Dwivedi et al, 1980;Omata et al, 1982), increased levels of mACh receptors (Coccini et al, 2000), and reduced concentrations of acetylcholine (ACh) (Hrdina et al, 1976;Kobayashi et al, 1980). Furthermore, some of the clinical outcomes of cholinergic dysfunction (i.e., anorexia, salivation, tremors, reduced vision, seizures) (Kobayashi et al, 1980;Wess, 2004) have also been observed in Hg-poisoned individuals (ATSDR, 1999; Watanabe and Satoh, 1996), thus suggesting a possible role for this neurotransmission system in the progression of MeHg toxicosis.…”

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confidence: 99%

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Methylmercury Impairs Components of the Cholinergic System in Captive Mink (Mustela vison)

Basu¹,

Scheuhammer²,

Rouvinen‐Watt³

et al. 2006

Toxicological Sciences

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The effects of methylmercury (MeHg) on components of the cholinergic system were evaluated in captive mink (Mustela vison). Cholinergic parameters were measured in brain regions (occipital cortex, cerebellum, brain stem, basal ganglia) and blood (whole blood, plasma, serum) following an 89-day exposure to MeHg at dietary concentrations of 0, 0.1, 0.5, 1, and 2 ppm (n = 12 animals per treatment). There were no effects of MeHg on brain choline acetyltransferase, acetylcholine, and choline transporter. However, significantly higher densities of muscarinic cholinergic receptors, as assessed by 3H-quinuclidinyl benzilate binding, were measured in the occipital cortex (30.2 and 39.0% higher in the 1 and 2 ppm groups, respectively), basal ganglia (67.5 and 69.1% higher in the 0.5 and 1 ppm groups, respectively), and brain stem (64.4% higher in the 0.5 ppm group), compared to nonexposed controls. The calculated positive relationship between MeHg exposure and muscarinic cholinergic receptor levels in this dosing study were consistent with observations in wild mink. There were no MeHg-related effects on blood cholinesterase (ChE) activity, but ChE activity was significantly higher in the occipital cortex (17.0% in the 1 ppm group) and basal ganglia (34.1% in the 0.5 ppm group), compared to nonexposed controls. The parallel increases in muscarinic cholinergic receptor levels and ChE activity following MeHg exposure highlight the autoregulatory nature of cholinergic neurotransmission. In conclusion, these laboratory data support findings from wild mink and demonstrate that ecologically relevant exposures to MeHg (i.e., 0.5 ppm in diet) have the potential to alter the cholinergic system in specific brain regions.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Methylmercury Impairs Components of the Cholinergic System in Captive Mink (Mustela vison)

Basu¹,

Scheuhammer²,

Rouvinen‐Watt³

et al. 2006

Toxicological Sciences

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“…Mercury is a nonspecific cytotoxic compound [45,46] and rodent studies have shown that organic and inorganic Hg can impair various aspects of neurotransmission. For example, laboratory rats [47] and mice [48] exposed to MeHg had decreased concentrations of brain acetylcholine, the primary agonist of the mACh receptor. Reduced acetylcholine levels, as a result of MeHg exposure, are supported by mechanistic studies demonstrating that MeHg can suppress the activity of choline acetyltransferase [25,26], inhibit the voltage‐gated entry of acetylcholine into pre‐ and postsynaptic nerve endings [49,50], and impair the binding of [ 3 H]‐QNB to the mACh receptor [31].…”

Section: Discussionmentioning

confidence: 99%

Effects of mercury on neurochemical receptor‐binding characteristics in wild mink

Basu

Klenavic

Gamberg³

et al. 2005

Enviro Toxic and Chemistry

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Piscivorous wildlife, such as mink (Mustela vison), routinely are exposed to mercury (Hg) in their natural environment at levels that may cause adverse behavioral outcomes. The purpose of this study was to determine if a correlation exists between neurochemical receptors and concentrations of Hg in the brains of wild mink. Specifically, receptor-binding assays were conducted to characterize the muscarinic cholinergic (mACh) and dopaminergic-2 (D2) systems in brain tissues collected from mink trapped in the Yukon Territory, Ontario, and Nova Scotia (Canada), and values were correlated with total Hg and methyl Hg (MeHg) concentrations in the brains. A significant correlation was found between Hg (total Hg and MeHg) and mACh receptor density (r = 0.546; r = 0.596, respectively) or ligand affinity (r = 0.413; r = 0.474, respectively). A significant negative correlation was found between total Hg and D2 receptor density (r = -0.340) or ligand affinity (r = -0.346). These correlations suggest that environmentally relevant concentrations of Hg may alter neurochemical function in wild mink, and that neurochemical receptor-binding characteristics can be used as a novel biomarker to assess Hg's effects on wildlife. Given the importance of the muscarinic cholinergic and dopaminergic pathways in animal behavior, further studies are required to explore the physiological and ecological significance of these findings.

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“…Longterm administration of MeHg slightly but uniformly decreases cerebral ChAT activity (13). As a result, the rate of ACh synthesis and the levels of regional ACh are decreased (14,15). In rats, prenatal exposure to MeHg reduced muscarinic binding in the developing brain (16).…”

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confidence: 99%

Low-Level Exposure to Methylmercury Modifies Muscarinic Cholinergic Receptor Binding Characteristics in Rat Brain and Lymphocytes: Physiologic Implications and New Opportunities in Biologic Monitoring

Coccini¹,

Randine²,

Candura³

et al. 2000

Environmental Health Perspectives

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Effect of methylmercury on brain acetylcholine concentration and turnover in mice

Cited by 25 publications

References 38 publications

Methylmercury Impairs Components of the Cholinergic System in Captive Mink (Mustela vison)

Methylmercury Impairs Components of the Cholinergic System in Captive Mink (Mustela vison)

Effects of mercury on neurochemical receptor‐binding characteristics in wild mink

Low-Level Exposure to Methylmercury Modifies Muscarinic Cholinergic Receptor Binding Characteristics in Rat Brain and Lymphocytes: Physiologic Implications and New Opportunities in Biologic Monitoring

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