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1.
Toxicol Sci ; 91(1): 202-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16446290

RESUMO

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.


Assuntos
Compostos de Metilmercúrio/farmacologia , Receptores Colinérgicos/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/metabolismo , Colina O-Acetiltransferase/metabolismo , Vison , Receptores Colinérgicos/metabolismo
2.
Environ Toxicol Chem ; 24(6): 1444-50, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16117121

RESUMO

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.


Assuntos
Encéfalo/metabolismo , Intoxicação por Mercúrio/metabolismo , Vison/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores Muscarínicos/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Exposição Ambiental , Feminino , Masculino , Mercúrio/farmacocinética , Nova Escócia , Ontário , Ensaio Radioligante , Yukon
3.
Environ Sci Technol ; 39(10): 3585-91, 2005 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-15952362

RESUMO

Fish-eating wildlife, such as river otters (Lontra canadensis), accumulate mercury (Hg) at concentrations known to impair animal behavior, but few studies have explored the underlying biochemical changes that precede clinical neurotoxicity. The objective of this study was to determine if Hg exposure can be related to concentrations of neurochemical receptors in river otters. River otter carcasses (n = 66) were collected in Ontario and Nova Scotia (Canada) by local trappers in 2002-2004. Concentrations of Hg (total and organic) were measured in the cerebral cortex and cerebellum. Saturation binding curves for the cholinergic muscarinic acetylcholine (mACh) receptor and dopamine-2 (D2) receptor were completed for each animal to calculate receptor density (Bmax) and ligand affinity (Kd). Negative correlations were found between concentrations of Hg and mACh receptor Bmax (r(total) Hg = -0.458, r(inorganic) Hg = -0.454, r(organic) Hg = -0.443) in the cerebral cortex. A negative correlation was also found between concentrations of total Hg and D2 receptor Bmax (r = -0.292) in the cerebral cortex. These results suggest that neurochemical receptors may prove useful as novel biomarkers of Hg exposure and neurotoxic effects in wildlife. Given the importance of cholinergic and dopaminergic systems in animal physiology, the ecological implications of these changes need to be investigated.


Assuntos
Mercúrio/metabolismo , Lontras/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores Muscarínicos/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Biomarcadores , Cerebelo/química , Cerebelo/metabolismo , Córtex Cerebral/química , Córtex Cerebral/metabolismo , Dieta , Antagonistas de Dopamina/farmacologia , Monitoramento Ambiental , Peixes , Mercúrio/análise , Antagonistas Muscarínicos/farmacologia , Nova Escócia , Ontário , Quinuclidinil Benzilato/farmacologia , Espiperona/farmacologia , Trítio , Poluentes Químicos da Água/análise
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