Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Dec;85(24):9821–9825. doi: 10.1073/pnas.85.24.9821

Localization of mRNA for low density lipoprotein receptor and a cholesterol synthetic enzyme in rabbit nervous system by in situ hybridization.

L W Swanson 1, D M Simmons 1, S L Hofmann 1, J L Goldstein 1, M S Brown 1
PMCID: PMC282873  PMID: 2462254

Abstract

The low density lipoprotein receptor and one of its ligands, apoprotein E, are known to be synthesized in the central nervous system. In the current study, we used in situ hybridization to localize the receptor mRNA in selected neurons and glia throughout the nervous system of 9-day-old rabbits. Particularly high levels were found in sensory ganglia, sensory nuclei, and motor-related nuclei. The same regions contained high levels of mRNA for 3-hydroxy-3-methylglutaryl-coenzyme A synthase, a regulated enzyme in cholesterol biosynthesis. The distribution of low density lipoprotein receptor mRNA was similar in mature and immature rabbits. The data suggest that certain cells in the nervous system have high requirements for cholesterol, which they satisfy through cholesterol synthesis and through receptor-mediated uptake of cholesterol-carrying lipoproteins. The latter originate in astrocytes which synthesize and secrete apoprotein E. These data suggest that the nervous system of mammals contains an active system for continuous redistribution and recycling of cholesterol that is physically distinct from the lipoprotein transport system in plasma.

Full text

PDF
9821

Images in this article

9822Image
on p.9822
9823Image
on p.9823
9824Image
on p.9824
9824Image
on p.9824
9824Image
on p.9824
9824Image
on p.9824

Selected References

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

  1. Arvidson B. Distribution of intravenously injected protein tracers in peripheral ganglia of adult mice. Exp Neurol. 1979 Feb;63(2):388–410. doi: 10.1016/0014-4886(79)90134-1. [DOI] [PubMed] [Google Scholar]
  2. Basu S. K., Brown M. S., Ho Y. K., Havel R. J., Goldstein J. L. Mouse macrophages synthesize and secrete a protein resembling apolipoprotein E. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7545–7549. doi: 10.1073/pnas.78.12.7545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boyles J. K., Pitas R. E., Wilson E., Mahley R. W., Taylor J. M. Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Invest. 1985 Oct;76(4):1501–1513. doi: 10.1172/JCI112130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown M. S., Goldstein J. L. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986 Apr 4;232(4746):34–47. doi: 10.1126/science.3513311. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Cox K. H., DeLeon D. V., Angerer L. M., Angerer R. C. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol. 1984 Feb;101(2):485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
  7. Dalal K. B., Einstein E. R. Biochemical maturation of the central nervous system. I. Lipid changes. Brain Res. 1969 Dec;16(2):441–451. doi: 10.1016/0006-8993(69)90237-6. [DOI] [PubMed] [Google Scholar]
  8. Dietschy J. M., Kita T., Suckling K. E., Goldstein J. L., Brown M. S. Cholesterol synthesis in vivo and in vitro in the WHHL rabbit, an animal with defective low density lipoprotein receptors. J Lipid Res. 1983 Apr;24(4):469–480. [PubMed] [Google Scholar]
  9. Gerfen C. R., Sawchenko P. E. An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L). Brain Res. 1984 Jan 9;290(2):219–238. doi: 10.1016/0006-8993(84)90940-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gil G., Goldstein J. L., Slaughter C. A., Brown M. S. Cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase from the hamster. I. Isolation and sequencing of a full-length cDNA. J Biol Chem. 1986 Mar 15;261(8):3710–3716. [PubMed] [Google Scholar]
  11. Hofmann S. L., Russell D. W., Goldstein J. L., Brown M. S. mRNA for low density lipoprotein receptor in brain and spinal cord of immature and mature rabbits. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6312–6316. doi: 10.1073/pnas.84.17.6312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Le Goascogne C., Robel P., Gouézou M., Sananès N., Baulieu E. E., Waterman M. Neurosteroids: cytochrome P-450scc in rat brain. Science. 1987 Sep 4;237(4819):1212–1215. doi: 10.1126/science.3306919. [DOI] [PubMed] [Google Scholar]
  13. Mahley R. W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988 Apr 29;240(4852):622–630. doi: 10.1126/science.3283935. [DOI] [PubMed] [Google Scholar]
  14. Mahley R. W., Innerarity T. L., Rall S. C., Jr, Weisgraber K. H. Plasma lipoproteins: apolipoprotein structure and function. J Lipid Res. 1984 Dec 1;25(12):1277–1294. [PubMed] [Google Scholar]
  15. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pitas R. E., Boyles J. K., Lee S. H., Hui D., Weisgraber K. H. Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J Biol Chem. 1987 Oct 15;262(29):14352–14360. [PubMed] [Google Scholar]
  17. Spady D. K., Dietschy J. M. Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat. J Lipid Res. 1983 Mar;24(3):303–315. [PubMed] [Google Scholar]
  18. Yamamoto T., Bishop R. W., Brown M. S., Goldstein J. L., Russell D. W. Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit. Science. 1986 Jun 6;232(4755):1230–1237. doi: 10.1126/science.3010466. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES