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. 1987 Nov;75:59–64. doi: 10.1289/ehp.877559

Metal toxicity in the central nervous system.

T W Clarkson 1
PMCID: PMC1474439  PMID: 3319566

Abstract

The nervous system is the principal target for a number of metals. Inorganic compounds of aluminum, arsenic, lead, lithium, manganese, mercury, and thallium are well known for their neurological and behavioral effects in humans. The alkyl derivatives of certain metals--lead, mercury and tin--are specially neurotoxic. Concern over human exposure and in some cases, outbreaks of poisoning, have stimulated research into the toxic action of these metals. A number of interesting hypotheses have been proposed for the mechanism of lead toxicity on the nervous system. Lead is known to be a potent inhibitor of heme synthesis. A reduction in heme-containing enzymes could compromise energy metabolism. Lead may affect brain function by interference with neurotransmitters such as gamma-amino-isobutyric acid. There is mounting evidence that lead interferes with membrane transport and binding of calcium ions. Methylmercury produces focal damage to specific areas in the adult brain. One hypothesis proposes that certain cells are susceptible because they cannot repair the initial damage to the protein sythesis machinery. The developing nervous system is especially susceptible to damage by methylmercury. It has been discovered that microtubules are destroyed by this form of mercury and this effect may explain the inhibition of cell division and cell migration, processes that occur only in the developmental stages. These and other hypotheses will stimulate considerable experimental challenges in the future.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe T., Haga T., Kurokawa M. Blockage of axoplasmic transport and depolymerisation of reassembled microtubules by methyl mercury. Brain Res. 1975 Mar 28;86(3):504–508. doi: 10.1016/0006-8993(75)90904-x. [DOI] [PubMed] [Google Scholar]
  2. Alfrey A. C., LeGendre G. R., Kaehny W. D. The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med. 1976 Jan 22;294(4):184–188. doi: 10.1056/NEJM197601222940402. [DOI] [PubMed] [Google Scholar]
  3. Atchison W. D., Narahashi T. Mechanism of action of lead on neuromuscular junctions. Neurotoxicology. 1984 Fall;5(3):267–282. [PubMed] [Google Scholar]
  4. Audesirk G. Effects of lead exposure on the physiology of neurons. Prog Neurobiol. 1985;24(3):199–231. doi: 10.1016/0301-0082(85)90006-1. [DOI] [PubMed] [Google Scholar]
  5. Betz A. L., Goldstein G. W. Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries. Science. 1978 Oct 13;202(4364):225–227. doi: 10.1126/science.211586. [DOI] [PubMed] [Google Scholar]
  6. Brennan M. J., Cantrill R. C. Delta-aminolaevulinic acid is a potent agonist for GABA autoreceptors. Nature. 1979 Aug 9;280(5722):514–515. doi: 10.1038/280514a0. [DOI] [PubMed] [Google Scholar]
  7. Charbonneau S. M., Munro I. C., Nera E. A., Armstrong F. A., Willes R. F., Bryce F., Nelson R. F. Chronic toxicity of methylmercury in the adult cat. Interim report. Toxicology. 1976 Mar;5(3):337–349. doi: 10.1016/0300-483x(76)90052-4. [DOI] [PubMed] [Google Scholar]
  8. Cheung M. K., Verity M. A. Experimental methyl mercury neurotoxicity: locus of mercurial inhibition of brain protein synthesis in vivo and in vitro. J Neurochem. 1985 Jun;44(6):1799–1808. doi: 10.1111/j.1471-4159.1985.tb07171.x. [DOI] [PubMed] [Google Scholar]
  9. Choi B. H., Lapham L. W., Amin-Zaki L., Saleem T. Abnormal neuronal migration, deranged cerebral cortical organization, and diffuse white matter astrocytosis of human fetal brain: a major effect of methylmercury poisoning in utero. J Neuropathol Exp Neurol. 1978 Nov-Dec;37(6):719–733. doi: 10.1097/00005072-197811000-00001. [DOI] [PubMed] [Google Scholar]
  10. Cooper G. P., Suszkiw J. B., Manalis R. S. Heavy metals: effects on synaptic transmission. Neurotoxicology. 1984 Fall;5(3):247–266. [PubMed] [Google Scholar]
  11. Egle P. M., Shelton K. R. Chronic lead intoxication causes a brain-specific nuclear protein to accumulate in the nuclei of cells lining kidney tubules. J Biol Chem. 1986 Feb 15;261(5):2294–2298. [PubMed] [Google Scholar]
  12. Gehring P. J., Hammond P. B. The interrelationship between thallium and potassium in animals. J Pharmacol Exp Ther. 1967 Jan;155(1):187–201. [PubMed] [Google Scholar]
  13. Goldstein G. W. Brain capillaries: a target for inorganic lead poisoning. Neurotoxicology. 1984 Fall;5(3):167–175. [PubMed] [Google Scholar]
  14. Goodwin F. K. The lithium ion -- impact on treatment and research: introduction. Arch Gen Psychiatry. 1979 Jul 20;36(8 Spec No):833–834. [PubMed] [Google Scholar]
  15. Goyer R. A., Leonard D. L., Moore J. F., Rhyne B., Krigman M. R. Lead dosage and the role of the intranuclear inclusion body. An experimental study. Arch Environ Health. 1970 Jun;20(6):705–711. doi: 10.1080/00039896.1970.10665647. [DOI] [PubMed] [Google Scholar]
  16. Goyer R. A., May P., Cates M. M., Krigman M. R. Lead and protein content of isolated intranuclear inclusion bodies from kidneys of lead-poisoned rats. Lab Invest. 1970 Mar;22(3):245–251. [PubMed] [Google Scholar]
  17. HUNTER D., RUSSELL D. S. Focal cerebellar and cerebellar atrophy in a human subject due to organic mercury compounds. J Neurol Neurosurg Psychiatry. 1954 Nov;17(4):235–241. doi: 10.1136/jnnp.17.4.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hirayama K. Effect of amino acids on brain uptake of methyl mercury. Toxicol Appl Pharmacol. 1980 Sep 15;55(2):318–323. doi: 10.1016/0041-008x(80)90093-9. [DOI] [PubMed] [Google Scholar]
  19. Hirayama K. Effects of combined administration of thiol compounds and methylmercury chloride on mercury distribution in rats. Biochem Pharmacol. 1985 Jun 1;34(11):2030–2032. doi: 10.1016/0006-2952(85)90328-4. [DOI] [PubMed] [Google Scholar]
  20. Holtzman D., DeVries C., Nguyen H., Olson J., Bensch K. Maturation of resistance to lead encephalopathy: cellular and subcellular mechanisms. Neurotoxicology. 1984 Fall;5(3):97–124. [PubMed] [Google Scholar]
  21. Jensen S., Jernelöv A. Biological methylation of mercury in aquatic organisms. Nature. 1969 Aug 16;223(5207):753–754. doi: 10.1038/223753a0. [DOI] [PubMed] [Google Scholar]
  22. Margolis R. L., Wilson L. Microtubule treadmills--possible molecular machinery. Nature. 1981 Oct 29;293(5835):705–711. doi: 10.1038/293705a0. [DOI] [PubMed] [Google Scholar]
  23. McKeown-Eyssen G. E., Ruedy J., Neims A. Methyl mercury exposure in northern Quebec. II. Neurologic findings in children. Am J Epidemiol. 1983 Oct;118(4):470–479. doi: 10.1093/oxfordjournals.aje.a113652. [DOI] [PubMed] [Google Scholar]
  24. McLachlin J. R., Goyer R. A., Cherian M. G. Formation of lead-induced inclusion bodies in primary rat kidney epithelial cell cultures: effect of actinomycin D and cycloheximide. Toxicol Appl Pharmacol. 1980 Dec;56(3):418–431. doi: 10.1016/0041-008x(80)90076-9. [DOI] [PubMed] [Google Scholar]
  25. Miura K., Suzuki K., Imura N. Effects of methylmercury on mitotic mouse glioma cells. Environ Res. 1978 Dec;17(3):453–471. doi: 10.1016/0013-9351(78)90048-8. [DOI] [PubMed] [Google Scholar]
  26. Moore J. F., Goyer R. A. Lead-induced inclusion bodies: composition and probable role in lead metabolism. Environ Health Perspect. 1974 May;7:121–127. doi: 10.1289/ehp.747121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Needleman H. L., Gunnoe C., Leviton A., Reed R., Peresie H., Maher C., Barrett P. Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N Engl J Med. 1979 Mar 29;300(13):689–695. doi: 10.1056/NEJM197903293001301. [DOI] [PubMed] [Google Scholar]
  28. PASSOW H., ROTHSTEIN A., CLARKSON T. W. The general pharmacology of the heavy metals. Pharmacol Rev. 1961 Jun;13:185–224. [PubMed] [Google Scholar]
  29. PETERS R. A. Biochemistry of some toxic agents. I. Present state of knowledge of biochemical lesions induced by trivalent arsenical poisoning. Bull Johns Hopkins Hosp. 1955 Jul;97(1):1–20. [PubMed] [Google Scholar]
  30. Pardridge W. M. Blood-brain transport of nutrients. Introduction. Fed Proc. 1986 Jun;45(7):2047–2049. [PubMed] [Google Scholar]
  31. Sager P. R., Aschner M., Rodier P. M. Persistent, differential alterations in developing cerebellar cortex of male and female mice after methylmercury exposure. Brain Res. 1984 Jan;314(1):1–11. doi: 10.1016/0165-3806(84)90170-6. [DOI] [PubMed] [Google Scholar]
  32. Sager P. R., Doherty R. A., Olmsted J. B. Interaction of methylmercury with microtubules in cultured cells and in vitro. Exp Cell Res. 1983 Jun;146(1):127–137. doi: 10.1016/0014-4827(83)90331-2. [DOI] [PubMed] [Google Scholar]
  33. Shellenberger M. K. Effects of early lead exposure on neurotransmitter systems in the brain. A review with commentary. Neurotoxicology. 1984 Fall;5(3):177–212. [PubMed] [Google Scholar]
  34. Silbergeld E. K., Lamon J. M. Role of altered heme synthesis in lead neurotoxicity. J Occup Med. 1980 Oct;22(10):680–684. doi: 10.1097/00043764-198010000-00016. [DOI] [PubMed] [Google Scholar]
  35. Silbergeld E. K., Wolinsky J. S., Goldstein G. W. Electron probe microanalysis of isolated brain capillaries poisoned with lead. Brain Res. 1980 May 12;189(2):369–376. doi: 10.1016/0006-8993(80)90097-9. [DOI] [PubMed] [Google Scholar]
  36. Thomas D. J., Smith J. C. Effects of coadministered low-molecular-weight thiol compounds on short-term distribution of methyl mercury in the rat. Toxicol Appl Pharmacol. 1982 Jan;62(1):104–110. doi: 10.1016/0041-008x(82)90106-5. [DOI] [PubMed] [Google Scholar]
  37. Walsh T. J., Tilson H. A. Neurobehavioral toxicology of the organoleads. Neurotoxicology. 1984 Fall;5(3):67–86. [PubMed] [Google Scholar]
  38. Yoshino Y., Mozai T., Nakao K. Biochemical changes in the brain in rats poisoned with an alkymercury compound, with special reference to the inhibition of protein synthesis in brain cortex slices. J Neurochem. 1966 Nov;13(11):1223–1230. doi: 10.1111/j.1471-4159.1966.tb04281.x. [DOI] [PubMed] [Google Scholar]

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