ToxSci Advance Access originally published online on January 30, 2006
Toxicological Sciences 2006 91(1):202-209; doi:10.1093/toxsci/kfj121
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Methylmercury Impairs Components of the Cholinergic System in Captive Mink (Mustela vison)
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* Department of Natural Resource Sciences, McGill University, Ste. Anne de Bellevue, Quebec, Canada, H9X 3V9;
Center for Indigenous Peoples' Nutrition and Environment (CINE), McGill University, Ste. Anne de Bellevue, Quebec, Canada, H9X 3V9;
Department of Plant and Animal Sciences and Canadian Centre for Fur Animal Research (CCFAR), Nova Scotia Agricultural College, Truro, Nova Scotia, Canada, B2N 5E3;
Environmental and Resource Studies, Trent University, Peterborough, Ontario, Canada, K9J 7B8; ¶ School of Dietetics and Human Nutrition, McGill University, Ste. Anne de Bellevue, Quebec, Canada, H9X 3V9; and || National Wildlife Research Center, Canadian Wildlife Service, Environment Canada, Ottawa, Ontario, Canada, K1A 0H3
Received December 21, 2005; accepted January 23, 2006
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.
Key Words: mink; methylmercury; muscarinic receptor; cholinesterase; brain; wildlife; neurotoxicology.
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