Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1977 Mar 1;72(3):604–616. doi: 10.1083/jcb.72.3.604

Myelinogenesis in optic nerve. A morphological, autoradiographic, and biochemical analysis

PMCID: PMC2111025  PMID: 138685

Abstract

Morphological, autoradiographic, and biochemical methods were used to study the time of appearance, distribution, and nature of sulfated constituents in the developing rat optic nerve. Electron microscope studies showed that myelination begins (6 days postnatal) shortly after the appearance of oligodendroglia (5 days postnatal). Over the ensuing 3 wk, myelination increased rapidly. During the 1st postnatal wk, mucopolysaccharides and glycoproteins were labeled with 35S and autoradiographs showed grains over arachnoidal cells, astroglia, and the glia limitans. These results indicated that astroglia synthesize sulfated mucopolysaccharides of the glia limitans. After the onset of myelination, however, the major portion of [35S]sulfate was incorporated into sulfatide. Autoradiographs showed a shift of radioactive grains from astroglia and arachnoidal cells to myelin, indicating that actively myelinating oligodendroglia incorporate [35S]sulfate into myelin sulfatide; there was a concomitant increase in the activity of cerebroside sulfotransferase. In addition, the increasing amounts of proteolipid protein and myelin basic protein corresponded with the morphological appearance of myelin. These results point to a strict correlation between the structural and biochemical changes occurring during myelination. This system provides a useful model for studies designed to evaluate the effects of various perturbations on the process of myelination.

Full Text

The Full Text of this article is available as a PDF (2.1 MB).

Selected References

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

  1. Adams D. H., Fox M. E. The homogeneity and protein composition of rat brain myelin. Brain Res. 1969 Aug;14(3):647–661. doi: 10.1016/0006-8993(69)90205-4. [DOI] [PubMed] [Google Scholar]
  2. Cohen S. R., McKhann G. M., Guarnieri M. A radioimmunoassay for myelin basic protein and its use for quantitative measurements. J Neurochem. 1975 Oct;25(4):371–376. doi: 10.1111/j.1471-4159.1975.tb04329.x. [DOI] [PubMed] [Google Scholar]
  3. Elam J. S., Goldberg J. M., Radin N. S., Agranoff B. W. Rapid axonal transport of sulfated mucopolysaccharide proteins. Science. 1970 Oct 23;170(3956):458–460. doi: 10.1126/science.170.3956.458. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Farrell D. F., McKhann G. M. Characterization of cerebroside sulfotransferase from rat brain. J Biol Chem. 1971 Aug 10;246(15):4694–4702. [PubMed] [Google Scholar]
  6. Fleischer B., Zambrano F. Localization of cerebroside-sulfotransferase activity in the Golgi apparatus of rat kidney. Biochem Biophys Res Commun. 1973 Jun 8;52(3):951–958. doi: 10.1016/0006-291x(73)91029-2. [DOI] [PubMed] [Google Scholar]
  7. Fleischhauer K., Wartenberg H. Elektronenmikroskopische Untersuchungen über das Wachstum der Nervenfasern und über das Auftreten von Markscheiden im Corpus callosum der Katze. Z Zellforsch Mikrosk Anat. 1967;83(4):568–581. [PubMed] [Google Scholar]
  8. Friede R. L., Samorajski T. Myelin formation in the sciatic nerve of the rat. A quantitative electron microscopic, histochemical and radioautographic study. J Neuropathol Exp Neurol. 1968 Oct;27(4):546–570. [PubMed] [Google Scholar]
  9. Fry J. M., Lehrer G. M., Bornstein M. B. Sulfatide synthesis: inhibition by experimental allergic encephalomyelitis serum. Science. 1972 Jan 14;175(4018):192–194. doi: 10.1126/science.175.4018.192. [DOI] [PubMed] [Google Scholar]
  10. GAZE R. M., PETERS A. The development, structure and composition of the optic nerve of Xenopus laevis (Daudin). Q J Exp Physiol Cogn Med Sci. 1961 Oct;46:299–309. doi: 10.1113/expphysiol.1961.sp001548. [DOI] [PubMed] [Google Scholar]
  11. George E., Singh M., Bachhawat B. K. The nature of sulphation of uronic acid-containing glycosaminoglycans catalysed by brain sulphotransferase. J Neurochem. 1970 Feb;17(2):189–200. doi: 10.1111/j.1471-4159.1970.tb02200.x. [DOI] [PubMed] [Google Scholar]
  12. Hedley-Whyte E. T. Distribution of [1,2-3H]cholesterol in mouse brain after injection in the suckling period. J Cell Biol. 1975 Aug;66(2):333–350. doi: 10.1083/jcb.66.2.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Herndon R. M., Rauch H. C., Einstein E. R. Immuno-electron microscopic localization of the encephalitogenic basic protein in myelin. Immunol Commun. 1973;2(2):163–172. doi: 10.3109/08820137309022789. [DOI] [PubMed] [Google Scholar]
  14. Hirose G., Bass N. H. Maturation of oligodendroglia and myelinogenesis in rat optic nerve: a quantitative histochemical study. J Comp Neurol. 1973 Nov 15;152(2):201–209. doi: 10.1002/cne.901520207. [DOI] [PubMed] [Google Scholar]
  15. Huttenlocher P. R. Myelination and the development of function in immature pyramidal tract. Exp Neurol. 1970 Dec;29(3):405–415. doi: 10.1016/0014-4886(70)90068-3. [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. MacBrinn M. C., O'Brien J. S. Lipid composition of optic nerve myelin. J Neurochem. 1969 Jan;16(1):7–12. doi: 10.1111/j.1471-4159.1969.tb10337.x. [DOI] [PubMed] [Google Scholar]
  18. Margolis R. K., Margolis R. U. Sulfated glycopeptides from rat brain glycoproteins. Biochemistry. 1970 Oct 27;9(22):4389–4396. doi: 10.1021/bi00824a020. [DOI] [PubMed] [Google Scholar]
  19. Margolis R. U., Margolis R. K. Distribution and metabolism of mucopolysaccharides and glycoproteins in neuronal perikarya, astrocytes, and oligodendroglia. Biochemistry. 1974 Jul 2;13(14):2849–2852. doi: 10.1021/bi00711a011. [DOI] [PubMed] [Google Scholar]
  20. Matheson D. F. Some aspects of lipid and protein metabolism in developing rat optic nerves. Brain Res. 1970 Dec 1;24(2):271–283. doi: 10.1016/0006-8993(70)90106-x. [DOI] [PubMed] [Google Scholar]
  21. Matheson D. F. Some quantitative aspects of myelination of the optic nerve in rat. Brain Res. 1970 Dec 1;24(2):257–269. doi: 10.1016/0006-8993(70)90105-8. [DOI] [PubMed] [Google Scholar]
  22. Matthews M. A., Duncan D. A quantitative study of morphological changes accompanying the initiation and progress of myelin production in the dorsal funiculus of the rat spinal cord. J Comp Neurol. 1971 May;142(1):1–22. doi: 10.1002/cne.901420102. [DOI] [PubMed] [Google Scholar]
  23. Matthieu J. M., Quarles R. H., Poduslo J. F., Brady R. O. [35-S]sulfate incorporation into myelin glycoproteinsmi=entral nervous system. Biochim Biophys Acta. 1975 May 5;392(1):159–166. doi: 10.1016/0304-4165(75)90176-2. [DOI] [PubMed] [Google Scholar]
  24. McHenry F. A., Hoffman P. N., Salpeter M. M. Uptake of 35S-sulfate by morphologically differentiated replicating chondrocytes in vivo: a double isotope electron microscope autoradiographic study. Dev Biol. 1974 Jul;39(1):96–104. doi: 10.1016/s0012-1606(74)80011-4. [DOI] [PubMed] [Google Scholar]
  25. McKhann G. M., Ho W. The in vivo and in vitro synthesis of sulphatides during development. J Neurochem. 1967 Jul;14(7):717–724. doi: 10.1111/j.1471-4159.1967.tb10305.x. [DOI] [PubMed] [Google Scholar]
  26. Morell P., Greenfield S., Costantino-Ceccarini E., Wisniewski H. Changes in the protein composition of mouse brain myelin during development. J Neurochem. 1972 Nov;19(11):2545–2554. doi: 10.1111/j.1471-4159.1972.tb01313.x. [DOI] [PubMed] [Google Scholar]
  27. Norton W. T., Poduslo S. E. Myelination in rat brain: changes in myelin composition during brain maturation. J Neurochem. 1973 Oct;21(4):759–773. doi: 10.1111/j.1471-4159.1973.tb07520.x. [DOI] [PubMed] [Google Scholar]
  28. Quarles R. H., Everly J. L., Brady R. O. Evidence for the close association of a glycoprotein with myelin in rat brain. J Neurochem. 1973 Nov;21(5):1177–1191. doi: 10.1111/j.1471-4159.1973.tb07573.x. [DOI] [PubMed] [Google Scholar]
  29. Rawlins F. A. A time-sequence autoradiographic study of the in vivo incorporation of (1,2-3H)cholesterol into peripheral nerve myelin. J Cell Biol. 1973 Jul;58(1):42–53. doi: 10.1083/jcb.58.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Salpeter M. M., Salpeter E. E. Resolution in electron microscope radioautography. II. Carbon 14. J Cell Biol. 1971 Aug;50(2):324–332. doi: 10.1083/jcb.50.2.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schlichter D. J., McClure W. O. Dynamics of axoplasmic transport in the optic system of the rat. Exp Brain Res. 1974;21(1):83–95. doi: 10.1007/BF00234259. [DOI] [PubMed] [Google Scholar]
  32. Silberberg D., Benjamins J., Herschkowitz N., McKhann G. M. Incorporation of radioactive sulphate into sulphatide during myelination in cultures of rat cerebellum. J Neurochem. 1972 Jan;19(1):11–18. doi: 10.1111/j.1471-4159.1972.tb01248.x. [DOI] [PubMed] [Google Scholar]
  33. Skoff R. P., Price D. L., Stocks A. Electron microscopic autoradiographic studies of gliogenesis in rat optic nerve. I. Cell proliferation. J Comp Neurol. 1976 Oct 1;169(3):291–312. doi: 10.1002/cne.901690303. [DOI] [PubMed] [Google Scholar]
  34. Skoff R. P., Price D. L., Stocks A. Electron microscopic autoradiographic studies of gliogenesis in rat optic nerve. II. Time of origin. J Comp Neurol. 1976 Oct 1;169(3):313–334. doi: 10.1002/cne.901690304. [DOI] [PubMed] [Google Scholar]
  35. Uzman B. G., Murray M. R., Saito H. Incorporation of (35S) sulfate into chondroitin sulfates by organized cultures of murine peripheral, sympathetic and central nervous tissues. J Neurobiol. 1973;4(5):429–441. doi: 10.1002/neu.480040504. [DOI] [PubMed] [Google Scholar]
  36. Wolf B. A., Robbins P. W. Cell mitotic cycle synthesis of NIL hamster glycolipids including the Forssman antigen. J Cell Biol. 1974 Jun;61(3):676–687. doi: 10.1083/jcb.61.3.676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wood P. M., Bunge R. P. Evidence that sensory axons are mitogenic for Schwann cells. Nature. 1975 Aug 21;256(5519):662–664. doi: 10.1038/256662a0. [DOI] [PubMed] [Google Scholar]
  38. Young R. W. The role of the Golgi complex in sulfate metabolism. J Cell Biol. 1973 Apr;57(1):175–189. doi: 10.1083/jcb.57.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zgorzalewicz B., Neuhoff V., Waehneldt T. V. Rat myelin proteins. Compositional changes in various regions of the nervous system during ontogenetic development. Neurobiology. 1974;4(5):265–276. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES