Chronic lead intoxication affects the myelin membrane status in the central nervous system of adult rats Authors
Cite this article as: Dabrowska-Bouta, B., Sulkowski, G., Bartosz, G. et al. J Mol Neurosci (1999) 13: 127. doi:10.1385/JMN:13:1-2:127 Abstract
The aim of the experiments presented here was to discern whether prolonged consumption of leaden water, which imitates an environmental exposure, affects the structure of myelin in the central nervous system of adult rats and whether the observed morphological destruction is reflected in biophysical and/or biochemical changes. The results indicated that during chronic lead (Pb) intoxication, the Pb level of the myelin fraction increases significantly. Electron microscopy studies show that myelin in control experiments is built up of ordered layers, whereas in a Pb-intoxicated sample, this order is destroyed in large areas of all preparations. Morphological disturbances in Pb-intoxicated in vivo myelin were reflected by changes in myelin membrane fluidity measured by spectrofluorometry and electron paramagnetic resonance (EPR). Prolonged Pb toxicity also caused significant changes in the morphological structure of oligodendrocytes, an increase of phosphatidylethanolamine, and decrease of protein SH group levels. Simultaneously, we found that the protein and total phospholipid content and levels of phosphatidylinositol, sphingomyelin, phosphatidyloserine, cholesterol, and the pattern of total myelin protein obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in Pb-intoxicated myelin did not change compared to control values. Also, Pb intoxication did not induce peroxidation by itself and did not accelerate peroxidation produced by iron (Fe) in brain myelin.
Index Entries Lead myelin membrane fluidity oligodendrocytes protein phospholipids SH groups peroxidation References
Asakawa T. and Matsushita S. (1980) Coloring conditions of thiobarbituric acid test for detecting lipid hydroperoxides.
Bartosz G., Szobo G., Szollosz J., Szollosz J., and Damjanovich S. (1981) Aging of the erythrocyte. IX Fluorescence studies on changes in membrane properties.
Mech. Ageing Dev.
Bligh E. G. and Dyer W. J. (1959) A rapid method of total lipid extraction and purification.
Can. J. Biochem. Physiol.
Bowman R. E. and Wolf R. C. (1962) A rapid and specific ultramicro method for serum cholesterol.
Bradbury M. W. B. and Deane R. (1993) Permeability of the blood-brain barrier to lead.
Braun P. E. (1977) Molecular architecture of myelin, in
Myelin (Morell P., ed.) Plenum, New York, pp. 91–113.
Butterfield D. A. (1977) Electron spin resonance studies of erythrocyte membranes in Muscular dystrophy.
Accts. Chem. Res.
Cory-Slechta D. A. and Wichowski D. V. (1991) Low level lead exposure increases sensitivity to this stimulus properties of dopamine D
Dabrowska-Bouta B., Strużyńska L., and Rafalowska U. (1996a) Effect of acute and chronic lead exposure on the level of sulfhydryl groups in rat brain.
Acta Neurobiol. Exp.
Dabrowska-Bouta B., Walski M., Jasińska R., Strużyńska L., Rafalowska U. (1996c) Morphological and biochemical changes in myelin after chronic lead exposure.
Int. J. Dev. Neurosci.
14 ( Suppl. 1), 96.
Dabrowska-Bouta B., Strużyńska L., and Rafalowska U. (1996d) Effect of acute and chronic lead exposure on the level of sulfhydryl groups in rat brain.
Acta Neurobiol. Exp.
Davis J. M., Elias R. W., and Grant L. D. (1993) Current issues in human lead exposure and regulation of lead.
Domańska-Janik K., Wihiel H., Zelman I., and Strosznajder J. (1986) Brain lipids of a myelin-deficient rabbit mutant during development.
Folch-Pi J. (1955) Composition of the brain in relation to maturation in biochemistry of the developing nervous system. (Waelched H., ed.) Acadia Press, New York, pp. 121–136.
Goering P. L. (1993) Lead-protein interactions as a basis for lead toxicity.
Grandjean P. (1993) International perspectives of lead exposure and lead toxicity.
Grant L. D., Kimmel C. S., West G. L. M., Nartinez-Vargas ChM., and Howard J. L. (1980) Chroniclow-level lead toxicity in the rat.
Toxicol. Appl. Pharm.
Harry G. J., Toews A. D., Krigman M. R., and Morell P. (1985) The effect of lead toxicity and milk deprivation on myelination in the rat.
Toxicol. Appl. Pharmacol.
Hubbell W. L. and McConnell H. U. (1971) Molecular motion in spin-labeled phospholipids and membranes.
J. Chem. Soc.
Jablońska L., Walski M., and Rafalowska U. (1994) Lead as an inductor of some morphological and functional changes in synaptosomes from rat brain.
Cell. Mol. Neurobiol.
Laemmli U. K. (1970) Cleavage of structural proteins during the assemble of the head of bacteriophage T4.
Litmon B. J. and Barenholz Y. (1982) Fluorescent probe: diphenylhexatiene.
London Y., Demel R. A., Geurts van Kessel W. S. M., Vossenberg F. G. A., and van Deenen L. L. M. (1973) The protection of A1 myelin basic protein against the action of proteolitic enzymes after interaction of the protein with lipids at the air-water interface.
Biochim. Biophys. Acta
Lowry O. H., Rosebrough N. J., Farr A. L., and Randall R. J. (1951) Protein measurements with Folin phenol reagent.
J. Biol. Chem.
McMorris F. A. and McKinnon R. D. (1996) Regulation of oligodendrocyte development and CNS myelination by growth factors: Prospects for therapy of demyelinating disease.
Melly-Goubert B. and Freedman M. H. (1980) Lipid fluidity and membrane protein monitoring using 1,6 diphenyl-1,3,5-hexatriene.
Biochem. Biophys. Acta
Morell P. (1994)
Principles of Neurotoxicology (Chang L. ed.) New York, pp. 583–605.
Morell P., Quorles R. H., and Norton W. T. (1989) Formation, structure and biochemistry of myelin, in
Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 4th ed., (Siegel, G. J. ed.) Raven, New York, pp 109–136.
Myher J. J., Kuksis A., and Pind S. (1989)
Needleman H. L. (1980) Low level lead exposure, in
The Clinical Implications of Current Research. Raven, New York.
Norton W. T. (1984)
Oligodendroglia. Plenum, New York.
Norton W. T. and Poduslo S. E. (1973) Myelination in rat brain: method of myelin isolation.
Quinlan G. J., Halliwell B., Moorhouse C. P., and Gutterdige J. M. (1988) Action of lead (II) and aluminium (III) ions on iron-stimulated lipid peroxidation in liposomes, erythrocytes and rat liver microsomal fractions.
Biochim. Biophys. Acta
Rafalowska U., Guang-Jun L., and Floyd R. A. (1989) Peroxidation induced changes in synaptosomal transport of dopamine and aminobutyric acid.
Free Radial. Biol. Med.
Rafalowska U., Strużyńska L., Dabrowska-Bouta B., and Lenkiewicz A. (1996) Is lead toxicosis a reflection of altered energy metabolism in brain synaptosomes?
Acta Neurobiol. Exp.
Raine C. S. (1984) Morphology of myelin and myelination, in
Myelin, 2nd ed. (Morell P., ed.) Plenum, New York, pp. 1–4.
Rouser G., Fleischer S., and Yamamoto A. (1970) Two dimensional thin layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots.
Sedlak J. and Lindsay R. H. (1968) Estimation of total, protein bound and non protein sulfhydryl groups in tissue with Ellman’s reagent.
Shinitzky R. and Inbar M. (1974) Difference in microviscosity induced by different cholesterol levels in the surface membrane lipid layer of normal lymphocytes and malignant lymphoma cells.
J. Mol. Biol.
Silbergeld E. K. (1983) Location of metals: Issues of importance to neurotoxicology of lead.
Skoczyńska A., Smolik R., and Jeleń M. (1993) Lipid abnormalities in rats given small doses of lead.
Strużyńska L., Walski M., Gadamski R., Dabrowska-Bouta B., and Rafalowska U. (1997) Lead-induced abnormalities in the blood-brain barrier permeability in experimental chronic toxicity.
Mol. Chem. Neuropathol.
Sundström R. and Karlsson B. (1987) Myelin basic protein in brains of rats with low dose lead encephalopathy.
Toews A. D., Krigman M. R., Thomas D. J., and Morell P. (1980) Effect of inorganic lead exposure on myelination in the rat.
Toews A. D., Blaker W. D., Thomas D. J., Gayonor J. J., Krigman M. R., Mushak P., et al. (1983) Myelin deficit produced by early postnatal exposure to inorganic lead or triethyltin are persistent.
Tschudy D. P. and Lamon J. M. (1980) in
Metabolic Disease and Control (Bandy P. K. and Rosenberg L. E., eds.) W. B. Saunders, Philadelphia, pp. 939–1007.
Wilbur K. M., Bernheim F., and Shapiro O. W. (1949) The thiobarbituric acid reagent as a test for the oxidation of unsaturated fatty acids by various agents.
Arch. Biochem. Biophys.