Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1974 May;7:187–199. doi: 10.1289/ehp.747187

Effect of Lead Intoxication on the Postnatal Growth of the Rat Nervous System*

Martin R Krigman, Edward L Hogan
PMCID: PMC1475147  PMID: 4831140

Abstract

Lead encephalopathy was induced in developing Long-Evans rats by adding lead carbonate (4% w/w) to the diet of nursing mother immediately after delivery. The morphological and biochemical features of cerebral ontogenesis were studied in 30-day-old rats.

By the 30th postnatal day, the overall effect of lead intoxication was retardation of brain growth. The mass of both the cerebral gray and white matter was appreciably reduced in the lead rats without any reduction in cell populations. While the neuronal population was preserved, the growth of neurons was reduced and their maturation retarded. The retarded neuronal growth was characterized by the limited proliferation of processes in the neuropil and by the reduction in the number of synapses per neuron. However, synaptogenesis was neither delayed nor perturbed but reduced by the limited development of neuronal dendritic fields. The myelination was altered and its cerebral content significantly reduced. The effect of lead on myelination was one of hypomyelination. The hypomyelination appears to be primarily related to retarded growth and maturation of the neuron and is not a reflection of a defect in the myelinating glia or a delay in the initiation of myelination.

Full text

PDF
187

Images in this article

191FIGURE 1.
on p.191

Selected References

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

  1. Altman J., Das G. D. Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J Comp Neurol. 1966 Mar;126(3):337–389. doi: 10.1002/cne.901260302. [DOI] [PubMed] [Google Scholar]
  2. Armstrong-James M., Johnson R. Quantitative studies of postnatal changes in synapses in rat superficial motor cerebral cortex. An electron microscopical study. Z Zellforsch Mikrosk Anat. 1970;110(4):559–568. doi: 10.1007/BF00330104. [DOI] [PubMed] [Google Scholar]
  3. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  4. BESSMAN S. P., LAYNE E. C., Jr A rapid procedure for the determination of lead in blood or urine in the presence of organic chelating agents. J Lab Clin Med. 1955 Jan;45(1):159–166. [PubMed] [Google Scholar]
  5. Caley D. W., Maxwell D. S. Development of the blood vessels and extracellular spaces during postnatal maturation of rat cerebral cortex. J Comp Neurol. 1970 Jan;138(1):31–47. doi: 10.1002/cne.901380104. [DOI] [PubMed] [Google Scholar]
  6. Cragg B. G. The density of synapses and neurones in the motor and visual areas of the cerebral cortex. J Anat. 1967 Sep;101(Pt 4):639–654. [PMC free article] [PubMed] [Google Scholar]
  7. David O., Clark J., Voeller K. Lead and hyperactivity. Lancet. 1972 Oct 28;2(7783):900–903. doi: 10.1016/s0140-6736(72)92534-2. [DOI] [PubMed] [Google Scholar]
  8. Davison A. N., Dobbing J. Myelination as a vulnerable period in brain development. Br Med Bull. 1966 Jan;22(1):40–44. doi: 10.1093/oxfordjournals.bmb.a070434. [DOI] [PubMed] [Google Scholar]
  9. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  10. HESS H. H., LEWIN E. MICROASSAY OF BIOCHEMICAL STRUCTURAL COMPONENTS IN NERVOUS TISSUES. II. METHODS FOR CEREBROSIDES, PROTEOLIPID PROTEINS AND RESIDUE PROTEINS. J Neurochem. 1965 Mar;12:205–211. doi: 10.1111/j.1471-4159.1965.tb06756.x. [DOI] [PubMed] [Google Scholar]
  11. Joseph K. C., Druse M. J., Newell L. R., Hogan E. L. Fatty acid composition of cerebrosides, sulphatides and ceramides in murine leucodystrophy: the quaking mutant. J Neurochem. 1972 Feb;19(2):307–312. doi: 10.1111/j.1471-4159.1972.tb01340.x. [DOI] [PubMed] [Google Scholar]
  12. Joseph K. C., Hogan E. L. Fatty acid composition of cerebrosides, sulphatides and ceramides in murine sudanophilic leucodystrophy: the Jimpy mutant. J Neurochem. 1971 Sep;18(9):1639–1645. doi: 10.1111/j.1471-4159.1971.tb03737.x. [DOI] [PubMed] [Google Scholar]
  13. Karlsson U. Comparison of the myelin period of peripheral and central origin by electron microscopy. J Ultrastruct Res. 1966 Jun;15(3):451–468. doi: 10.1016/s0022-5320(66)80118-1. [DOI] [PubMed] [Google Scholar]
  14. Kurokawa M., Kato M., Sakamoto T. Distribution of sodium-plus-potassium-stimulated adenosine-triphosphatase activity in isolated nerve-ending particles. Biochem J. 1965 Dec;97(3):833–844. doi: 10.1042/bj0970833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LOWDEN J. A., WOLFE L. S. STUDIES ON BRAIN GANGLIOSIDES. 3. EVIDENCE FOR THE LOCATION OF GANGLIOSIDES SPECIFICALLY IN NEURONES. Can J Biochem. 1964 Nov;42:1587–1594. doi: 10.1139/o64-170. [DOI] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Lin-Fu J. S. Undue absorption of lead among children--a new look at an old problem. N Engl J Med. 1972 Mar 30;286(13):702–710. doi: 10.1056/NEJM197203302861306. [DOI] [PubMed] [Google Scholar]
  18. MORRISON W. R., SMITH L. M. PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. J Lipid Res. 1964 Oct;5:600–608. [PubMed] [Google Scholar]
  19. MacMillan V. H., Wherrett J. R. A modified procedure for the analysis of mixtures of tissue gangliosides. J Neurochem. 1969 Dec;16(12):1621–1624. doi: 10.1111/j.1471-4159.1969.tb10361.x. [DOI] [PubMed] [Google Scholar]
  20. Norton W. T., Autilio L. A. The lipid composition of purified bovine brain myelin. J Neurochem. 1966 Apr;13(4):213–222. doi: 10.1111/j.1471-4159.1966.tb06794.x. [DOI] [PubMed] [Google Scholar]
  21. O'Brien J. S., Sampson E. L. Fatty acid and fatty aldehyde composition of the major brain lipids in normal human gray matter, white matter, and myelin. J Lipid Res. 1965 Oct;6(4):545–551. [PubMed] [Google Scholar]
  22. Pentschew A., Garro F. Lead encephalo-myelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases. With special reference to the permeability disorders of the nervous system's capillaries. Acta Neuropathol. 1966 Jun 1;6(3):266–278. doi: 10.1007/BF00687857. [DOI] [PubMed] [Google Scholar]
  23. Rosenblum W. I., Johnson M. G. Neuropathologic changes produced in suckling mice by adding lead to the maternal diet. Arch Pathol. 1968 Jun;85(6):640–648. [PubMed] [Google Scholar]
  24. SUZUKI K. A SIMPLE AND ACCURATE MICROMETHOD FOR QUANTITATIVE DETERMINATION OF GANGLIOSIDE PATTERNS. Life Sci. 1964 Nov;3:1227–1233. doi: 10.1016/0024-3205(64)90040-2. [DOI] [PubMed] [Google Scholar]
  25. Suzuki K., Poduslo S. E., Norton W. T. Gangliosides in the myelin fraction of developing rats. Biochim Biophys Acta. 1967 Oct 2;144(2):375–381. doi: 10.1016/0005-2760(67)90166-x. [DOI] [PubMed] [Google Scholar]
  26. VOELLER K., PAPPAS G. D., PURPURA D. P. Electron microscope study of development of cat superficial neocortex. Exp Neurol. 1963 Feb;7:107–130. doi: 10.1016/s0014-4886(63)80003-5. [DOI] [PubMed] [Google Scholar]
  27. Valverde F. Apical dendritic spines of the visual cortex and light deprivation in the mouse. Exp Brain Res. 1967;3(4):337–352. doi: 10.1007/BF00237559. [DOI] [PubMed] [Google Scholar]
  28. WEIBEL E. R., GOMEZ D. M. A principle for counting tissue structures on random sections. J Appl Physiol. 1962 Mar;17:343–348. doi: 10.1152/jappl.1962.17.2.343. [DOI] [PubMed] [Google Scholar]
  29. Weibel E. R. Stereological principles for morphometry in electron microscopic cytology. Int Rev Cytol. 1969;26:235–302. doi: 10.1016/s0074-7696(08)61637-x. [DOI] [PubMed] [Google Scholar]
  30. Winick M. Nutrition and nerve cell growth. Fed Proc. 1970 Jul-Aug;29(4):1510–1515. [PubMed] [Google Scholar]
  31. Zeman W. Presidential address: Studies in the neuronal ceroid-lipofuscinoses. J Neuropathol Exp Neurol. 1974 Jan;33(1):1–12. doi: 10.1097/00005072-197401000-00001. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES