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Variation of cholinergic biomarkers in brain regions and blood components of captive mink

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Abstract

Studies are increasingly using cholinergic parameters as biomarkers of early neurotoxicity, but few have characterized this system in ecologically relevant model organisms. In the present study, key neurochemicals in the cholinergic pathway were measured and analyzed from discrete parts of brain and blood from captive mink (Mustela vison). Similar to other mammals, the regional distribution of cholinergic parameters in the brain could be ranked from highest to lowest as: basal ganglia > occipital cortex > brain stem > cerebellum (F 3,192 = 172.1, p < 0.001). Higher variation in cholinergic parameters was found in the cerebellum (coefficient of variation = 34.9%), and the least variation was measured in the brain stem (19.7%). Variation was also assessed by calculating the difference between the lowest and highest measures among individual animals: choline acetyltransferase (1.6× fold difference), cholinesterase (2.0×), muscarinic receptor levels (2.4×), acetylcholine (3.7×), nicotinic receptor levels (3.9×), and choline transporter (5.0×). In blood samples, activity and inter-individual variation of cholinesterase was highest in whole blood and lowest in plasma and serum. By using captive mink of a common genetic source, age, gender, and rearing conditions, these data help establish normal levels, ranges, and variations of cholinergic biomarkers among brain regions, blood components, and individual animals. Such information may better enable the utility of cholinergic biomarkers in environmental assessments.

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References

  • Abou-Donia, M. B. (2003). Organophosphorus ester-induced chronic neurotoxicity. Archives of Environmental Health, 58, 484–497. doi:10.3200/AEOH.58.8.484-497.

    Article  CAS  Google Scholar 

  • Basu, N., Klenavic, K., Gamberg, M., O’Brien, M., Evans, R. D., Scheuhammer, A. M., et al. (2005a). Effects of mercury on neurochemical receptor binding characteristics in wild mink. Environmental Toxicology and Chemistry, 24, 1444–1450. doi:10.1897/04-048R.1.

    Article  CAS  Google Scholar 

  • Basu, N., Kwan, M., & Chan, H. M. (2006a). Mercury but not organochlorines inhibit muscarinic cholinergic receptor binding in the cerebrum of ringed seals (Phoca hispida). Journal of Toxicology and Environmental Health, 69, 1133–1143. doi:10.1080/15287390500362394.

    Article  CAS  Google Scholar 

  • Basu, N., Scheuhammer, A. M., Bursian, S. J., Elliott, J., Rouvinen-Watt, K., & Chan, H. M. (2007). Mink as a sentinel in environmental health. Environmental Research, 103, 130–144. doi:10.1016/j.envres.2006.04.005.

    Article  CAS  Google Scholar 

  • Basu, N., Scheuhammer, A. M., Grochowina, N., Klenavic, K., Evans, D., O’Brien, M., et al. (2005b). Effects of mercury on neurochemical receptors in wild river otters (Lontra canadensis). Environmental Science & Technology, 39, 3585–3591. doi:10.1021/es0483746.

    Article  CAS  Google Scholar 

  • Basu, N., Scheuhammer, A. M., Rouvinen-Watt, K., Grochowina, N., Klenavic, K., Evans, R. D., et al. (2006b). Methylmercury impairs components of the cholinergic system in captive mink (Mustela vison). Toxicological Sciences, 91, 202–209. doi:10.1093/toxsci/kfj121.

    Article  CAS  Google Scholar 

  • Bradford, M. M. (1976). A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248–254. doi:10.1016/0003-2697(76)90527-3.

    Article  CAS  Google Scholar 

  • Coccini, T., Randine, G., Candura, S. M., Nappi, R. E., Prockop, L. D., & Manzo, L. (2000). Low-level exposure to methylmercury modifies muscarinic cholinergic receptor binding characteristics in rat brain and lymphocytes: Physiologic implications and new opportunities in biologic monitoring. Environmental Health Perspectives, 108, 29–33. doi:10.2307/3454292.

    Article  CAS  Google Scholar 

  • Coccini, T., Randine, G., Castoldi, A. F., Grandjean, P., Ostendorp, G., Heinzow, B., et al. (2006). Effects of developmental co-exposure to methylmercury and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) on cholinergic muscarinic receptors in rat brain. Neurotoxicology, 27, 468–477. doi:10.1016/j.neuro.2005.12.004.

    Article  CAS  Google Scholar 

  • Dajas-Bailador, F., & Wonnacott, S. (2004). Nicotinic acetylcholine receptors and the regulation of neuronal signalling. Trends in Pharmacological Sciences, 25, 317–324. doi:10.1016/j.tips.2004.04.006.

    Article  CAS  Google Scholar 

  • Dietl, M. M., Cortés, R., & Palacios, J. M. (1988). Neurotransmitter receptors in the avian brain. II. Muscarinic cholinergic receptors. Brain Research, 439, 360–365.

    Google Scholar 

  • Fonnum, F. (1975). A rapid radiochemical method for the determination of choline acetyltransferase. Journal of Neurochemistry, 24, 407–409. doi:10.1111/j.1471-4159.1975.tb11895.x.

    Article  CAS  Google Scholar 

  • Goldberg, A. M., & Hanin, I. (1976). Biology of cholinergic function. New York: Raven.

    Google Scholar 

  • Gupta, R. (2004). Brain regional heterogeneity and toxicological mechanisms of organophosphates and carbamates. Toxicology Mechanisms and Methods, 14, 103–143. doi:10.1080/15376520490429175.

    Article  CAS  Google Scholar 

  • Gupta, R. C., Patterson, G. T., & Dettbarn, W. D. (1991). Comparison of cholinergic and neuromuscular toxicity following acute exposure to sarin and VX in rat. Fundamental and Applied Toxicology, 16, 449–458. doi:10.1016/0272-0590(91)90085-I.

    Article  CAS  Google Scholar 

  • Jett, D. A., Hill, E. F., Fernando, J. C., Eldefrawi, M. E., & Eldefrawi, A. T. (1993). Down-regulation of muscarinic receptors and the m3 subtype in white-footed mice by dietary exposure to parathion. Journal of Toxicology and Environmental Health, 39, 395–415

    Article  CAS  Google Scholar 

  • Jones, S. B., King, L. B., Sappington, L. C., Dwyer, F. J., Ellersieck, M., & Buckler, D. R. (1998). Effects of carbaryl, permethrin, 4-nonylphenol, and copper on muscarinic cholinergic receptors in brain of surrogate and listed fish species. Comparative Biochemistry and Physiology, 120(Pt C), 405–414.

    CAS  Google Scholar 

  • McGehee, D. S., & Role, L. W. (1995). Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annual Review of Physiology, 57, 521–546. doi:10.1146/annurev.ph.57.030195.002513.

    Article  CAS  Google Scholar 

  • McQueen, M. J. (1995). Clinical and analytical considerations in the utilization of cholinesterase measurements. Clinica Chimica Acta, 237, 91–105. doi:10.1016/0009-8981(95)06067-N.

    Article  CAS  Google Scholar 

  • Mineau, P. (1991). Cholinesterase-inhibiting insecticides. Amsterdam: Elsevier Science.

    Google Scholar 

  • Oda, Y. (1999). Choline acetyltransferase: The structure, distribution and pathologic changes in the central nervous system. Pathology International, 49, 921–937. doi:10.1046/j.1440-1827.1999.00977.x.

    Article  CAS  Google Scholar 

  • Okudza, T., & Haga, T. (2003). High-affinity choline transporter. Neurochemical Research, 28, 483–488. doi:10.1023/A:1022809003997.

    Article  Google Scholar 

  • Rozengart, E. V., Khovanskikh, A. E., Basoval, N. E., Moralev, S. N. (2003). Comparative enzymologic study of catalytic properties of blood serum cholinesterase of the American mink Mustela vison. Journal of Evolutionary Biochemistry and Physiology, 38, 401–406. doi:10.1023/A:1021145602100.

    Article  Google Scholar 

  • Salvaterra, P. M., Mahler, H. R., & Moore, W. J. (1975). Subcellular and regional distribution of 125I-labeled alpha-bungarotoxin binding in rat brain and its relationship to acetylcholinesterase and choline acetyltransferase. The Journal of Biological Chemistry, 250, 6469–6475.

    CAS  Google Scholar 

  • Silman, I., & Sussman, J. L. (2005). Acetylcholinesterase: ‘Classical’ and ‘non-classical’ functions and pharmacology. Current Opinion in Pharmacology, 5, 293–302. doi:10.1016/j.coph.2005.01.014.

    Article  CAS  Google Scholar 

  • Stavinoha, W. B., Weintraub, S. T., & Modak, A. T. (1973). The use of microwave heating to inactivate cholinesterase in the rat brain prior to analysis for acetylcholine. Journal of Neurochemistry, 20, 361–371. doi:10.1111/j.1471-4159.1973.tb12135.x.

    Article  CAS  Google Scholar 

  • Szabó, A., Nencsók, J., Kása, P., & Gulya, K. (1989). Muscarinic cholinergic components in carp brain. Neurochemistry International, 15, 511–516. doi:10.1016/0197-0186(89)90171-X.

    Article  Google Scholar 

  • Trauth, J. A., Seidler, F. J., McCook, E. C., & Slotkin, T. A. (1999). Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions. Brain Research, 851, 9–19. doi:10.1016/S0006-8993(99)01994-0.

    Article  CAS  Google Scholar 

  • Venter, J. C., Eddy, B., Hall, L. M., & Fraser, C. M. (1984). Monoclonal antibodies detect the conservation of muscarinic cholinergic receptor structure from Drosophila to human brain and detect possible structural homology with alpha 1-adrenergic receptors. Proceedings of the National Academy of Sciences of the United States of America, 81, 272–276. doi:10.1073/pnas.81.1.272.

    Article  CAS  Google Scholar 

  • Vickroy, T., Roeske, W., & Yamamura, H. (1984). Sodium-dependent high-affinity binding of [3H]hemicholinium-3 in the rat brain: A potentially selective marker for presynaptic cholinergic sites. Life Sciences, 35, 2335–2343. doi:10.1016/0024-3205(84)90525-3.

    Article  CAS  Google Scholar 

  • Wess, J. (1996). Molecular biology of muscarinic acetylcholine receptors. Critical Reviews in Neurobiology, 10, 69–99.

    CAS  Google Scholar 

  • Wess, J. (2004). Muscarinic acetylcholine receptor knockout mice: Novel phenotypes and clinical implications. Annual Review of Pharmacology and Toxicology, 44, 423–450. doi:10.1146/annurev.pharmtox.44.101802.121622.

    Article  CAS  Google Scholar 

  • Wessler, I., Kirkpatrick, C. J., & Racke, K. (1999). The cholinergic ‘pitfall’: Acetylcholine, a universal cell molecule in biological systems, including humans. Clinical and Experimental Pharmacology & Physiology, 26, 198–205. doi:10.1046/j.1440-1681.1999.03016.x.

    Article  CAS  Google Scholar 

  • Yamamura, H. I., & Snyder, S. H. (1974). Muscarinic cholinergic binding in rat brain. Proceedings of the National Academy of Sciences of the United States of America, 71, 1725–1729. doi:10.1073/pnas.71.5.1725.

    Article  CAS  Google Scholar 

  • Zanoli, P., Truzzi, C., Veneri, C., Braghiroli, D., & Baraldi, M. (1994). Methyl mercury during late gestation affects temporarily the development of cortical muscarinic receptors in rat offspring. Pharmacology & Toxicology, 75, 261–264.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA

    Niladri Basu

  2. National Wildlife Research Center, Canadian Wildlife Service, Environment Canada, Ottawa, Ontario, Canada, K1A 0H3

    Anton Scheuhammer

  3. Department of Plant and Animal Sciences and Canadian Centre for Fur Animal Research (CCFAR), Nova Scotia Agricultural College, Truro, Nova Scotia, Canada, B2N 5E3

    Kirsti Rouvinen-Watt

  4. Environmental and Resource Studies, Trent University, Peterborough, Ontario, Canada, K9J 7B8

    Nicole Grochowina & Douglas Evans

  5. Community Health Program, University of Northern British Columbia, Prince George, BC, Canada, V2N 4Z9

    Hing Man Chan

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  1. Niladri Basu
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  2. Anton Scheuhammer
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  3. Kirsti Rouvinen-Watt
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  4. Nicole Grochowina
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  5. Douglas Evans
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  6. Hing Man Chan
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Correspondence to Niladri Basu.

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Basu, N., Scheuhammer, A., Rouvinen-Watt, K. et al. Variation of cholinergic biomarkers in brain regions and blood components of captive mink. Environ Monit Assess 162, 377–386 (2010). https://doi.org/10.1007/s10661-009-0803-2

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  • DOI: https://doi.org/10.1007/s10661-009-0803-2

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