Decreased N-methyl-D-aspartic acid (NMDA) receptor levels are associated with mercury exposure in wild and captive mink.
Mercury (Hg) impairs glutamate homeostasis but little is known about its effects on the N-methyl-d-aspartic acid (NMDA) receptor. Here, we investigated NMDA receptor levels, as determined by [(3)H]-MK801 binding, in both wild and captive mink (Mustela vison) that experienced different levels of methylmercury (MeHg) exposure. Competitive in vitro binding experiments showed that inorganic Hg (HgCl(2); IC(50)=1.5-20.7 microM), but not MeHg (MeHgCl; IC(50)>320 microM), inhibited binding to the NMDA receptor in several brain regions of mink. In a survey of trapped wild mink, NMDA receptor levels in the brain were negatively correlated (p<0.005) with concentrations of total Hg (R=-0.618) and MeHg (R=-0.714). These findings were supported by a laboratory feeding study in which captive mink were exposed to dietary MeHg (0-2 ppm) for 89 days. Concentration-dependent decreases in NMDA receptor levels were found in the basal ganglia, cerebellum, brain stem and occipital cortex. These findings are of physiological and ecological concern because they demonstrate that Hg, at dietary concentrations as low as 0.1 ppm, can significantly reduce NMDA receptor levels.
Basu
Niladri
N
National Wildlife Research Center, Canadian Wildlife Service, Environment Canada, 1125 Colonel By Drive (Raven Road), Ottawa, Ontario, Canada. nbasu@uottawa.ca
Scheuhammer
Anton M
AM
Rouvinen-Watt
Kirsti
K
Grochowina
Nicole
N
Evans
R Douglas
RD
O'Brien
Mike
M
Chan
Hing Man
HM
D000818:Animals; D000835:Animals, Wild; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004032:Diet; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006207:Half-Life; D016014:Linear Models; D008628:Mercury / Q000378:metabolism / Q000633:toxicity; D020262:Mercury Poisoning, Nervous System / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000378:metabolism / Q000633:toxicity; D008907:Mink / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D008767:Methylmercury Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008628:Mercury