The Effects of Chronic Low-level Lead Exposure on the Early Structuring of the Central Nervous System

  • C. M. Regan
  • G. R. Cookman
  • G. J. Keane
  • W. King
  • S. E. Hemmens

Summary

Chronic low-level lead exposure has been demonstrated to inhibit neural cell acquisition and impair early postnatal structuring of the central nervous system. Lead was demonstrated to have an anti-mitotic action both in vitro and in vivo, although the latter was confined to the cerebellum at blood lead threshold values of 30–40 µg/dl. Low-level lead exposure more potently affected in vivo cell positioning and fibre outgrowth, as judged by the impaired developmental desialylation of the D2-CAM/N-CAM protein, and these effects were seen at blood lead threshold values of 20–30 µg/dl. This inhibition of normal D2-CAM/N-CAM desialylation is attributed to improper guidance of neuronal cells and their fibres, as lead is demonstrated to specifically induce precocious differentiation of the glial cells.

Keywords

Glutamine Synthetase Lead Exposure Neural Cell Adhesion Molecule Blood Lead Level Glutamine Synthetase Activity 
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References

  1. Averill, D. R. and Needleman, H. L. (1980) Neonatal lead exposure retards cortical synaptogenesis in the rat. In Needleman, H. (ed.), Low Level Lead Exposure: the Clinical Implications of Current Research, pp. 201 - 210 ( New York: Raven Press )Google Scholar
  2. Bailey, C. and Kitchen, I. (1985) Ontogenesis of proenkephalin products in rat striatum and the inhibitory effects of low level lead exposure. Dev. Brain Res., 22, 75–79CrossRefGoogle Scholar
  3. Bjerrum, O. J. and Bog-Hansen, T. C. (1976) Immunochemical gel precipitation in membrane studies. In Maddy, A. H. (ed.), Biochemical Analysis of Membrane, pp. 378–427. ( London: Chapman & Hall )Google Scholar
  4. Brackenbury, R., Thiery, J.-P., Rutishauser, U. and Edelman, G. M. (1977) Adhesion among neural cells of the chick embryo. I. An immunological assay for molecules involved in cell- cell binding. J. Biol Chem., 253, 7314–7318Google Scholar
  5. Buskirk, D. R., Thiery, J.-P., Rutishauser, U. and Edelman, G. M. (1980) Antibodies to a neural cell adhesion molecule disrupt histogenesis in cultured chick retinae. Nature, 285, 488–489PubMedCrossRefGoogle Scholar
  6. Bull, R. J., McCauley, P. T., Taylor, D. H. and Croften, K. M. (1983) The effects of lead onthe developing central nervous system of the rat. Neurotoxicology, 4, 1–18PubMedGoogle Scholar
  7. Choung, C.-M. and Edelman, G. M. (1984). Alterations in neural cell adhesion molecules during development of different regions of the nervous system. J. Neurosci., 4, 2354–2368Google Scholar
  8. Cory-Slechta, D. A. and Thompson, T. (1979) Behavioural toxicity of chronic post weaninglead exposure in the rat. Toxicol. Appl. Pharmacol, 47, 151–159PubMedCrossRefGoogle Scholar
  9. Edelman, G. M. (1985) Cell adhesion and the molecular processes of morphogenesis. Ann. Rev. Biochem., 54, 135–169PubMedCrossRefGoogle Scholar
  10. Edelman, G. M. and Chuong, C.-M. (1982) Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mice. Proc. Natl. Acad. Sci., 79, 7036–740PubMedCrossRefGoogle Scholar
  11. lsdale, T. and Bard, J. (1972) Collagen substrata for studies of cell behaviour. J. Cell Biol, 54, 626–637PubMedCrossRefGoogle Scholar
  12. Gross-Selbeck, E. and Gross-Selbeck, M. (1981) Changes in operant behaviour of rats exposed to lead at the accepted no-effect level. Clin. Toxicol, 18, 1247–1256PubMedCrossRefGoogle Scholar
  13. Hoffman, S. and Edelman, G. M (1983) Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc. Natl Acad. Sci. USA, 89, 5762–5766CrossRefGoogle Scholar
  14. Jacobson, M. (1978) Developmental Neurobiology, 2nd edn ( New York and London: Plenum )Google Scholar
  15. Kirk, D. L. (1965). The role of RNA synthesis in the production of glutamine synthetase by developing chick neural retina. Proc. Natl Acad. Sci. USA, 54, 1345–1353PubMedCrossRefGoogle Scholar
  16. Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. (1951) Protein measurement with the Folin reagent. J. Biol Chem., 193, 265–275PubMedGoogle Scholar
  17. McCauley, P. T. Bull, R. J., Tonti, A. P., Lutkenhoff, S. D., Meister, M. V., Doerger, J. U. and Stober, J. A. (1982) The effect of prenatal and postnatal lead exposure on neonatal synaptogenesis in rat cerebral cortex. J. Toxicol Env. Health, 10, 639–651CrossRefGoogle Scholar
  18. Meier, E., Regan, C., Balazs, R. and Wilkin, G. P. (1982) Specific recognition of the neuronal cell surface by an antiserum raised against a plasma membrane preparation of immature rat cerebellum. Neurochem. Res., 7, 1031–1043PubMedCrossRefGoogle Scholar
  19. Meier, E., Regan, C. M. and Balazs, R. (1984) Changes in the expression of a neuronal surface protein during development of cerebellar neurones in vivo and in culture. J. Neurochem., 43, 1328–1334PubMedCrossRefGoogle Scholar
  20. Needleman, H. L., Gunnoe, C, Leviton, A., Reed, M., Peresie, H., Maher, C. and Barrett, P. (1979) Deficits in psychological and classroom performance of children with elevated dentine lead levels. N Engl. J. Med., 300, 689–695PubMedCrossRefGoogle Scholar
  21. Norenberg, M. D. and Martinez-Hernandez, A. (1979) Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res., 161, 303–310PubMedCrossRefGoogle Scholar
  22. Pentschew, A. and Garro, F. (1966) Lead encephalomyelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases. Acta Neuropathol., 6, 266–278PubMedCrossRefGoogle Scholar
  23. Phelan, P. and Regan, C. M. (1982) Developmental expression of glutamine synthetase activity in rat brain. Ir. J. Med. Sci., 151, 403–404Google Scholar
  24. Rakic, P. and Sidman, R. L. (1971) Guidance of neurons migrating to the foetal monkey neocortex. Brain Res., 33, 471–476PubMedCrossRefGoogle Scholar
  25. Regan, C. M. (1985) Therapeutic levels of sodium valproate inhibits mitotic indices in cells of neural origin. Brain Res., 347, 394–398PubMedCrossRefGoogle Scholar
  26. Rutishauser, U., Gall, W. E. and Edelman, G. M. (1978) Adhesion among neural cells of the chick embryo. IV. Role of the cell surface molecule CAM in the formation of neurite bundles in cultures of spinal ganglia. J. Cell Biol., 79, 382–393PubMedCrossRefGoogle Scholar
  27. Rutter, M. (1980) Raised lead levels and impaired cognitive/behavioural functioning: a review of the evidence. Dev. Med. Child. Neurol, 22 (Suppl. 42), 1–26Google Scholar
  28. Sheehan, M. C., Halpin, C. I., Regan, C. M., Moran, N. M. and Kilty, C. G. (1986) Purification and characterisation of the D2 cell adhesion protein: analysis of the postnatally regulated polymorphic forms and their cellular distribution. Neurochem. Res., 11, 1343–1356CrossRefGoogle Scholar
  29. Sundstrom, R., Conrad, N. G. and Sourander, P. (1983). Low dose lead encephalopathy in the suckling rat. Acta Neuropathol, 60, 1–8PubMedCrossRefGoogle Scholar
  30. Taylor, D. H., Noland, E. A. Brubaker, C. M., Croften, K. M. and Bull, R. J. (1982) Low level lead (Pb) exposure produces learning deficits in young rat pups. Neurobehav. Toxicol Teratol, 4, 311–314PubMedGoogle Scholar
  31. Weeke, B. (1973) A manual of quantitative immunoelectrophoresis. Methods and applications. 1. General remarks and principles, equipment, reagents and procedures. Scand. J. Immunol, 2 (Suppl. 1), 15–35CrossRefGoogle Scholar
  32. Wenzel, J., Kammerer, E., Joschko, R., Joschko, M., Kaufmann, W., Kirsche, W. and Matthies, H. (1977) The influence of a learning experience on synaptosomes in the rat hippocampus. Z. Mikrosk.-Anat. Forsch., Leipzig, 91, 57–73Google Scholar
  33. Winneke, G. (1986) Animal studies. In Lansdown, R. and Yule, W. (eds), The Lead Debate: the Environment, Toxicology and Child Health, pp. 217–234 ( London: Croom Helm )Google Scholar
  34. Winneke, G., Brockhaus, A. and Baltissen, R. (1977) Neurobehavioural and systemic effects of longterm blood lead-elevation in rats. I. Discrimination learning and open field behaviour. Arch. Toxicol, 37, 247–263PubMedCrossRefGoogle Scholar
  35. Winneke, G., Hrdina, K.-G. and Brockhaus, A. (1982) Neuropsychological studies in children with elevated tooth-lead concentrations. I. Pilot study. Int. Arch. Occup. Env. Health, 51, 169–183CrossRefGoogle Scholar
  36. Winneke, G., Kramer, U., Brockhaus, A., Ewers, U., Kujanek, G., Lechner, H. and Janke, W. (1983) Neuropsychological studies in children with elevated tooth-lead concentrations. II. Extended study. Int. Arch. Occup. Env. Health, 51, 231–252CrossRefGoogle Scholar
  37. Yule, W. (1986) Methodological and statistical issues. In Lansdowne, R. and Yule, W. (eds), The Lead Debate: The Environment, Toxicology and Child Health, pp. 193–216 ( London: Croom Helm )Google Scholar
  38. Yule, W., Lansdown, R., Millar, I. B. and Urbanowicz, M.A. (1981) The relationship between blood lead concentrations, intelligence and attainment in a school population: a pilot study. Dev. Med. Child. Neurol, 23, 567–576PubMedCrossRefGoogle Scholar

Copyright information

© ECSC-EEC-EAEC, Brussels — Luxembourg; EPA, USA 1989

Authors and Affiliations

  • C. M. Regan
  • G. R. Cookman
  • G. J. Keane
  • W. King
  • S. E. Hemmens

There are no affiliations available

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