Cholinesterase and monoamine oxidase activity in relation to mercury levels in the cerebral cortex of wild river otters

Abstract

Mercury (Hg) is a global pollutant that is neurotoxic to many mammalian species. The present study was conducted to determine if the bioaccumulation of Hg by wild river otters (Lontra canadensis) could be related to variations in the activities of key neurochemical enzymes. River otters were collected from Ontario and Nova Scotia (Canada) during the trapping seasons, spanning 2002-2004, and their brains were dissected into the cerebral cortex and cerebellum. The activities of cholinesterase (ChE) and monoamine oxidase (MAO) were measured from each sample and correlated with concentrations of brain Hg from the same animal. Significant negative correlations were found between concentrations of brain Hg and ChE (total Hg: r= -0.42; MeHg: r= -0.33) and MAO (total Hg: r= -0.31; MeHg: r= -0.42) activity in the cerebral cortex. The scatterplots relating concentrations of brain Hg and enzyme activity in the cerebral cortex were wedge-shaped, and could be fitted with quantile regression modeling, suggesting that Hg may act as a limiting factor for ChE and MAO activity. No relationships were found in the cerebellum. These data suggest that environmentally relevant concentrations of Hg may influence the activities of ChE and MAO in the cerebral cortex of river otters, and by extension, other fish-eating mammals.

Keywords

brain enzymes mercury neurotoxicology wildlife

References

Taylor P , Radic R . The cholinesterases: from genes to proteins. Ann Rev Pharmacol Toxicol 1994; 34: 281-320.

Kuhar MJ , Couceyro PR , Lambert PD . Catecholamines. In Siegel GJ , Agranoff BW , Albers RW , Fisher SK , Uhler MD eds. Basic neurochemistry: molecular, cellular, and medical aspects. Lippincott Williams & Wilkins, 1988.

McDonald BE , Costa LG , Murphy SD . Spatial memory impairment and central muscarinic receptor loss following prolonged treatment with organophosphates. Toxicol Letts 1988; 40: 47-56.

Chakrabarti SK , Loua KM , Bai C , Durham H , Panisset JC . Modulation of monoamine oxidase activity in different brain regions and platelets following exposure of rats to methylmercury. Neurotoxicol Teratol 1998; 20: 161-168.

Berntssen MH , Aatland A , Handy RD . Chronic dietary mercury exposure causes oxidative stress, brain lesions, and altered behaviour in Atlantic salmon (Salmo salar) parr. Aquat Toxicol 2003; 65: 55-72.

Sandahl JF , Baldwin, DH , Jenkins JJ , Scholz NL . Comparative thresholds for acetylcholinesterase inhibition and behavioral impairment in coho salmon exposed to chlorpyrifos. Environ Toxicol Chem 2005; 24: 136-145.

Agency for Toxic Substances and Disease Registry (ATSDR) . Toxicological profile for mercury. US Department of Health and Human Services, 1999.

Clarkson TW . The toxicology of mercury. Crit Rev Clin Lab Sci 1997; 34: 369-403.

Manzo L , Artigas F , Martinez E , Mutti A , Bergamaschi E , Nicotera P , Tonini M , Candura SM , Ray DE , Costa LG . Biochemical markers of neurotoxicity. A review of mechanistic studies and applications. Hum Exp Toxicol 1996; 15: 20-35.

10.

Castoldi AF , Coccini T , Ceccatelli S , Manzo L . Neurotoxicity and molecular effects of methylmercury. Brain Res Bull 2001; 55: 197-203.

11.

Tsuzuki Y . Effect of chronic methylmercury exposure on activities of neurotransmitter enzymes in rat cerebellum. Toxicol Appl Pharmacol 1981; 60: 379-381.

12.

Shaw BP , Panigrahi AK . Brain AChE activity studies in some fish species collected from a mercury contaminated estuary. Water Air Soil Poll 1990; 53: 327-334.

13.

Zhou T , Rademacher DJ , Steinpreis RE , Weiss JS . Neurotransmitter levels in two populations of larval Fundulus heteroclitus after methylmercury exposure. Comp Biochem Physiol Part C 1999; 124: 287-294.

14.

Zabinski Z , Dabrowski Z , Moszczynski P , Rutowski J . The activity of erythrocyte enzymes and basic indices of peripheral blood erythrocytes from workers chronically exposed to mercury vapours. Toxicol Ind Health 2000; 16: 58-64.

15.

Stamler CJ , Abdelouahab N , Vanier C , Mergler D , Chan HM . Relationship between platelet monoamine oxidase-B (MAO-B) activity and mercury exposure in fish consumers from the Lac St. Pierre region of Que., Canada. Neurotoxicology 2006; in press.

16.

Chan HM , Scheuhammer AM , Ferran A , Loupelle C , Holloway J , Weech S . Impacts of mercury on freshwater fish-eating wildlife and humans. Hum Ecol Risk Assess 2003; 9: 867-883.

17.

Wiener JG , Krabbenhoft DP , Heinz GH , Scheuhammer AM . Ecotoxicology of mercury. In Hoffman DJ , Rattner BA , Burton GA Jr , Cairns J Jr eds. Handbook of ecotoxicology. CRC Press, 2003: 409-463.

18.

Basu N , Klenavic K , Gamberg M , O'Brien M , Evans RD , Scheuhammer AM , Chan HM . Effects of mercury on neurochemical receptor binding characteristics in wild mink. Environ Toxicol Chem 2005; 24: 1444-1450.

19.

Basu N , Scheuhammer AM , Grochowina NM , Klenavic K , Evans RD , O'Brien M , Chan HM . Effects of mercury on neurochemical receptors in wild river otters (Lontra canadensis). Environ Sci Technol 2005; 39: 3585-3591.

20.

Stamler CJ , Basu N , Chan HM . Biochemical markers of neurotoxicity in wildlife and human populations: considerations for method development. J Toxicol Environ Health 2005; 68: 1413-1429.

21.

Burn JD , Leighton FA . Further studies of brain cholinesterase: cholinergic receptor ratios in the diagnosis of acute lethal poisoning of birds by anticholinesterase pesticides. J Wildlife Dis 1996; 32: 216-224.

22.

Bradford MM . A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254.

23.

Stamler CJ , Arrieta D , Basu N , Henderson JD , Wilson BW , Chan HM . Evaluation of a fluorescent method for measuring cholinesterase activity in mammalian blood and tissue. Bull Environ Contam Toxicol 2006; under review.

24.

Drevnick PE , Sandheinrich MB . Effects of dietary methylmercury on reproductive endocrinology of fathead minnows. Environ Sci Technol 2003; 37: 4390-4396.

25.

Goldowitz D , Hamre K . The cells and molecules that make a cerebellum. Trends Neurosci 1998; 21: 375-382.

26.

Siegel GJ , Agranoff BW , Albers RW , Fisher SK , Uhler MD . Basic neurochemistry: molecular, cellular, and medical aspects. Lippincott Williams & Wilkins, 1988.

27.

Abou-Donia MB . Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health 2003; 58: 484-497.

28.

Kobayashi H , Yuyama A , Matsusaka N , Takeno K , Yanagiya I . Effects of methylmercury chloride on various cholinergic parameters in vitro. J Toxicol Sci 1979; 4: 351-362.

29.

Omata S , Hirakawa W , Daimon Y , Uchiyama M , Nakashita H , Horigome T , Sugano I , Sugano H . Methylmercury-induced changes in the activities of neurotransmitter enzymes in nervous tissues of the rat. Arch Toxicol 1982; 51: 285-294.

30.

Basu N , Stamler CJ , Loua KM , Chan HM . An interspecies comparison of mercury inhibition on muscarinic acetylcholine receptor binding in the cerebral cortex and cerebellum. Toxicol Appl Pharmacol 2005; 205: 71-76.

31.

Castoldi AF , Candura SM , Costa P , Manzo L , Costa LG . Interaction of mercury compounds with muscarinic receptor subtypes in the rat brain. Neurotoxicology 1996; 17: 735-741.

32.

Devi M , Fingerman M . Inhibition of acetylcholinesterase activity in the central nervous system of the red swamp crayfish, Procambarus clarkii, by mercury, cadmium, and lead. Bull Environ Contam Toxicol 1995; 55: 746-750.

33.

Duysen EG , Stribley JA , Fry DL , Hinrichs SH , Lockridge O . Rescue of the acetylcholinesterase knockout mouse by feeding a liquid diet; phenotype of the adult acetylcholinesterase deficient mouse. Dev Brain Res 2002; 137: 43-54.

34.

Costa LG , Schwab BW , Murphy SD . Tolerance to anticholinesterase compounds in mammals. Toxicology 1982; 25: 79-97.

35.

Liu J , Olivier K , Pope CN . Comparative neurochemical effects of repeated methyl parathion or chlorpyrifos exposures in neonatal and adult rats. Toxicol Appl Pharmacol 1999; 158: 186-196.

36.

Basu N , Scheuhammer AM , Rouvinen-Watt K , Grochowina N , Klenavic K , Evans RD , Chan HM . Methylmercury impairs components of the cholinergic system in captive mink (Mustela vison). Toxicol Sci 2006; 91: 202-209.

37.

Haines KJR , Evans RD , O'Brien M . Relationship between mercury and selenium in the brain of river otter (Lutra canadensis) and wild mink (Mustela vison) from Nova Scotia, Canada. Mater Geoenviron 2004; 51: 1028-1030.

38.

Faro LR , Duran R , Do Nascimento JL , Perez-Vences D , Alfonso M . Effects of successive intrastriatal methylmercury administrations on dopaminergic system. Ecotoxicol Environ Saf 2003; 55: 173-177.

39.

Hrdina PD , Peters DA , Singhal RL . Effects of chronic exposure to cadmium, lead and mercury of brain biogenic amines in the rat. Res Commun Chem Pathol Pharmacol 1976; 15: 483-493.

40.

Beyrouty P , Stamler CJ , Liu J-N , Loua KM , Kubow S , Chan HM . Effects of prenatal methylmercury exposure on brain monoamine oxidase activity and neurobehaviour of rats. Neurotoxicol Teratol 2006; 28: 251-259.

41.

Rajanna B , Hobson M . Influence of mercury on uptake of [3H]dopamine and [3H]norepinephrine by rat brain synaptosomes. Toxicol Letts 1985; 27: 7-14.

42.

Missale C , Nash SR , Robinson SW , Jaber M , Caron MG . Dopamine receptors: from structure to function. Physiol Rev 1998; 78: 189-225.

43.

Hammerschmidt CR , Sandheinrich MB , Wiener JG , Rada RG . Effects of dietary methylmercury on reproduction of fathead minnows. Environ Sci Technol 2002; 36: 877-883.

44.

Barr JF . Population dynamics of the common loon (Gavia immer) associated with mercury-contaminated waters in northwestern Ontario. Canadian Wildlife Service Occasional Paper No. 56 (CW69-1/56E), 1986.