Skip to main content
Log in

Origin of cholesterol in myelin

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

We review some of the older literature concerning metabolic turnover of cholesterol in the nervous system. The overall picture is that incorporation of radioactive precursors into brain cholesterol is roughly proportional to the rate of myelination and that, once incorporated, radioactive cholesterol is relatively stable metabolically. We outline a strategy for demonstrating the source (local synthesis or uptake from the circulation) of cholesterol in brain. The experimental design involves determining the rate of accumulation of cholesterol this is calculated as the increasing amounts of sterol in brain at successive time intervals during development. The rate of appearance of newly synthesized cholesterol is determined from incorporation of radioactivity from3H2O (injected i.p. several hours prior to sacrifice) into cholesterol. The radioactivity associated with the sterol fractions and the specific activity of body water determined from the serum can be used to calculate the absolute amount of sterol newly synthesized during the time when3H2O was present. The results obtained demonstrated that all of the bulk cholesterol accumulating in brain can be accounted for by newly synthesized cholesterol. None of the radioactive cholesterol came from the circulation, since cholesterol feeding suppressed cholesterol biosynthesis in the liver and specific radioactivity of circulating cholesterol was negligible. Thus, almost all cholesterol accumulating in brain during development is locally synthesized.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dietschy, J. M., and Spady, D. K. 1984. Measurement of rates of cholesterol synthesis using tritiated water. J. Lipid Res. 25:1469–1476.

    PubMed  CAS  Google Scholar 

  2. Morell, P., Quarles, R. H., and Norton, W. T. 1993. Myelin formation, structure, and biochemistry. Pages 117–143,in Albers, R. W., Siegel, G. W., Molinoff, P., and Agranoff, B. (eds.), Basic Neurochemistry. 5th Edition. Raven Press, New York.

    Google Scholar 

  3. Haque, Z. U., and Mozaffor, Z. 1992. Importance of dietary cholesterol for the maturation of mouse brain myelin. Biosci. Biotech. Biochem. 56:1351–1354.

    Article  CAS  Google Scholar 

  4. Acosta, P. B. 1994. RSH/SLO (Smith-Lemli-Opitz) syndrome: Designing a high cholesterol diet for the SLO syndrome. Am. J. of Med. Genet. 50:358–363.

    Article  CAS  Google Scholar 

  5. Smith, M. E. 1987. The metabolism of myelin lipids. Adv. in Lipid Res. 5:241–278.

    Google Scholar 

  6. Waelsch, H., Sperry, W. M., and Stoyanoff, V. A. 1941. The influence of growth and demyelination on the deposition and metabolism of lipids in the brain. J. Biol. Chem. 140:885–897.

    CAS  Google Scholar 

  7. Davison, A. N. 1965. Brain sterol metabolism. Adv. Lipid Res. 3: 171–196.

    PubMed  CAS  Google Scholar 

  8. Smith, M. E. 1973. A regional survey of myelin development: some compositional and metabolic aspects. J. Lipid Res. 14:541–551.

    PubMed  CAS  Google Scholar 

  9. Rawlins, F. A., and Smith, M. E. 1971. Myelin synthesis in vitro: A comparative study of central and peripheral nervous tissue. J. Neurochem. 18:1861–1870.

    Article  PubMed  CAS  Google Scholar 

  10. Smith, M. E., and Eng, L. F. 1965. The turnover of the lipid components of myelin. J. of the Am. Oil Chemists’ Soc. 42:1013–1018.

    CAS  Google Scholar 

  11. Davison, A. N., Dobbing, J., Morgan, R. S., and Wright, G. P. 1958. The deposition and disposal of (4-14C) cholesterol in the brain of growing chickens. J Neurochem. 3:89–94.

    PubMed  CAS  Google Scholar 

  12. Davison, A. N., and Wajda, M. 1959. Persistence of cholesterol-4-14C in the central nervous system. Nature (London) 183:1606–1607.

    Article  CAS  Google Scholar 

  13. Kritchevsky, D., and Defendi, V. 1962. Deposition of tritium labelled sterols (cholesterol, sitosterol, lanosterol) in brain and other organs of the growing chicken. J. Neurochem. 9:421–425.

    Article  PubMed  CAS  Google Scholar 

  14. Dobbing, J. 1963. The entry of cholesterol into rat brain during development. J. Neurochem. 10:739–742.

    Article  CAS  Google Scholar 

  15. Edmond, J., Korsak, R. A., Morrow, J. W., Torok-Both, G., and Catlin, D. H. 1991. Dietary cholesterol and the origin of cholesterol in the brain of developing rats. J. Nutr. 121:1323–1330.

    PubMed  CAS  Google Scholar 

  16. Andersen, J. M., and Dietschy, J. M. 1979. Absolute rates of cholesterol synthesis in extrahepatic tissues measured with3H labeled water and14C labeled substrates. J. Lipid Res. 20:740–752.

    PubMed  CAS  Google Scholar 

  17. Jurevics, H. A., and Morell, P. 1994. Sources of cholesterol for kidney and nerve during development. J. Lipid Res. 35:112–120.

    PubMed  CAS  Google Scholar 

  18. Jurevics, H., and Morell, P. 1995. Cholesterol for synthesis of myelin is made locally, not imported into brain. J. Neurochem. 64:895–901.

    Article  PubMed  CAS  Google Scholar 

  19. Wagner-Recio M., Toews, A. D., and Morell, P. 1991. Tellurium blocks cholesterol synthesis by inhibiting squalene metabolism: Preferential vulnerability to this metabolic block leads to peripheral nervous system demyelination. J. Neurochem. 57:1891–1901.

    Article  PubMed  CAS  Google Scholar 

  20. Toews, A. D., Goodrum, J. F., Lee, S. Y., Eckermann, C., and Morell, P. 1991. Tellurium-induced alterations in HMG-CoA reductase gene expression and enzyme activity: Differential effects in sciatic nerve and liver suggest tissue-specific regulation of cholesterol synthesis. J. Neurochem. 57:1902–1906.

    Article  PubMed  CAS  Google Scholar 

  21. Irons, M., Elias, E. R., Salen, G, Tint, G. S., and Batta, A. K. 1993. Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome. Lancet 341:1414.

    Article  PubMed  CAS  Google Scholar 

  22. Tint, G. S., Irons, M., Elias, E. R., Batta, A. K., Frieden, R., Chen, T. S., and Salen, G. S. 1994. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. New Eng. J. of Med. 330:107–113.

    Article  CAS  Google Scholar 

  23. Barness, L. A. 1994. Nutritional requirements of infants and children with respect to cholesterol and related compounds. Am. J. of Med. Genet. 50:353–354.

    Article  CAS  Google Scholar 

  24. Irons, M., Elias, E. R., Tint, G. S., Salen, G, Frieden, R., Buie, T. M., and Ampola, M. 1994. Abnormal cholesterol metabolism in the Smith-Lemli-Opitz syndrome: Report of clinical and biochemical findings in four patients and treatment in one patient. Am. J. of Med. Genet. 50:347–352.

    Article  CAS  Google Scholar 

  25. Nwokoro, N. A., Hyde, B., and Mulvihill, J. J. 1994. Smith-Lemli-Opitz Syndrome: Biochemical before clinical diagnosis; early dietary management. Am. Jour. of Med. Genet. 50:375–376.

    Article  CAS  Google Scholar 

  26. Smith, M. E., and Hasinoff, C. M. 1970. Inhibitors of cholesterol synthesis and myelin formation. Lipids 5:665–671.

    Article  PubMed  CAS  Google Scholar 

  27. Suzuki, K., and DePaul, L. D. 1971. Cellular degeneration in developing central nervous system of rats produced by hypocholesteremic drug AY9944. Lab. Invest. 25:546–555.

    PubMed  CAS  Google Scholar 

  28. Roux, C., Horvath, C., and Depuis, R. 1979. Teratogenic action and embryo lethality of AY9944: Prevention by a hypercholesterolemia-provoking diet. Teratology 19:35–38.

    Article  PubMed  CAS  Google Scholar 

  29. Barbu, V., Roux, C., Lambert, D., Duphis, R., Gardette, J., Maziere, J.-C., Maziere, C., Elefant, R., and Polonovski, J. 1988. Cholesterol prevents the teratogenic action of AY9944: Importance of the timing of cholesterol supplementation to rats. J. Nutr. 118:774–779.

    PubMed  CAS  Google Scholar 

  30. Xu, G., Salen, G., Shefer, S., Ness, G. C., Chen, T. S., Zhao, Z., and Tint, G. S. 1995. Reproducing abnormal cholesterol biosynthesis as seen in the Smith-Lemli-Opitz syndrome by inhibiting the conversion of 7-dehydrocholesterol to cholesterol in rats. J. Clin. Invest. 95:76–81.

    Article  PubMed  CAS  Google Scholar 

  31. Lakshmanan, M. R., and Veech, R. L. 1977. Measurement of rate of rat liver sterol synthesis in vivo using tritiated water. J. Biol. Chem. 252:4667–4673.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pierre Morell.

Additional information

Special issue dedicated to Dr. Marion R. Smith.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morell, P., Jurevics, H. Origin of cholesterol in myelin. Neurochem Res 21, 463–470 (1996). https://doi.org/10.1007/BF02527711

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02527711

Key Words

Navigation