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):9811–9815. doi: 10.1073/pnas.85.24.9811

Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain.

W C Mobley 1, R L Neve 1, S B Prusiner 1, M P McKinley 1
PMCID: PMC282871  PMID: 2904679

Abstract

Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the beta protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the beta-protein precursor (beta-PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and beta-PP mRNAs. The increases in PrP and beta-PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and beta-PP mRNA levels. Increased PrP and beta-PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and beta-PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes.

Full text

PDF
9811

Images in this article

9812Image
on p.9812
9813Image
on p.9813
9814Image
on p.9814

Selected References

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

  1. Auburger G., Heumann R., Hellweg R., Korsching S., Thoenen H. Developmental changes of nerve growth factor and its mRNA in the rat hippocampus: comparison with choline acetyltransferase. Dev Biol. 1987 Apr;120(2):322–328. doi: 10.1016/0012-1606(87)90235-1. [DOI] [PubMed] [Google Scholar]
  2. Bahmanyar S., Higgins G. A., Goldgaber D., Lewis D. A., Morrison J. H., Wilson M. C., Shankar S. K., Gajdusek D. C. Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease. Science. 1987 Jul 3;237(4810):77–80. doi: 10.1126/science.3299701. [DOI] [PubMed] [Google Scholar]
  3. Barry R. A., Prusiner S. B. Monoclonal antibodies to the cellular and scrapie prion proteins. J Infect Dis. 1986 Sep;154(3):518–521. doi: 10.1093/infdis/154.3.518. [DOI] [PubMed] [Google Scholar]
  4. Basler K., Oesch B., Scott M., Westaway D., Wälchli M., Groth D. F., McKinley M. P., Prusiner S. B., Weissmann C. Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell. 1986 Aug 1;46(3):417–428. doi: 10.1016/0092-8674(86)90662-8. [DOI] [PubMed] [Google Scholar]
  5. Carlson G. A., Kingsbury D. T., Goodman P. A., Coleman S., Marshall S. T., DeArmond S., Westaway D., Prusiner S. B. Linkage of prion protein and scrapie incubation time genes. Cell. 1986 Aug 15;46(4):503–511. doi: 10.1016/0092-8674(86)90875-5. [DOI] [PubMed] [Google Scholar]
  6. Cathala G., Savouret J. F., Mendez B., West B. L., Karin M., Martial J. A., Baxter J. D. A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983;2(4):329–335. doi: 10.1089/dna.1983.2.329. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Feramisco J. R., Smart J. E., Burridge K., Helfman D. M., Thomas G. P. Co-existence of vinculin and a vinculin-like protein of higher molecular weight in smooth muscle. J Biol Chem. 1982 Sep 25;257(18):11024–11031. [PubMed] [Google Scholar]
  10. Gajdusek D. C. Unconventional viruses and the origin and disappearance of kuru. Science. 1977 Sep 2;197(4307):943–960. doi: 10.1126/science.142303. [DOI] [PubMed] [Google Scholar]
  11. Glenner G. G., Wong C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984 May 16;120(3):885–890. doi: 10.1016/s0006-291x(84)80190-4. [DOI] [PubMed] [Google Scholar]
  12. Gnahn H., Hefti F., Heumann R., Schwab M. E., Thoenen H. NGF-mediated increase of choline acetyltransferase (ChAT) in the neonatal rat forebrain: evidence for a physiological role of NGF in the brain? Brain Res. 1983 Jul;285(1):45–52. doi: 10.1016/0165-3806(83)90107-4. [DOI] [PubMed] [Google Scholar]
  13. Goedert M. Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease. EMBO J. 1987 Dec 1;6(12):3627–3632. doi: 10.1002/j.1460-2075.1987.tb02694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goldgaber D., Lerman M. I., McBride O. W., Saffiotti U., Gajdusek D. C. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science. 1987 Feb 20;235(4791):877–880. doi: 10.1126/science.3810169. [DOI] [PubMed] [Google Scholar]
  15. Johnston M. V., Rutkowski J. L., Wainer B. H., Long J. B., Mobley W. C. NGF effects on developing forebrain cholinergic neurons are regionally specific. Neurochem Res. 1987 Nov;12(11):985–994. doi: 10.1007/BF00970927. [DOI] [PubMed] [Google Scholar]
  16. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  18. Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature. 1988 Feb 11;331(6156):530–532. doi: 10.1038/331530a0. [DOI] [PubMed] [Google Scholar]
  19. Kretzschmar H. A., Prusiner S. B., Stowring L. E., DeArmond S. J. Scrapie prion proteins are synthesized in neurons. Am J Pathol. 1986 Jan;122(1):1–5. [PMC free article] [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Large T. H., Bodary S. C., Clegg D. O., Weskamp G., Otten U., Reichardt L. F. Nerve growth factor gene expression in the developing rat brain. Science. 1986 Oct 17;234(4774):352–355. doi: 10.1126/science.3764415. [DOI] [PubMed] [Google Scholar]
  22. Leonard D. G., Gorham J. D., Cole P., Greene L. A., Ziff E. B. A nerve growth factor-regulated messenger RNA encodes a new intermediate filament protein. J Cell Biol. 1988 Jan;106(1):181–193. doi: 10.1083/jcb.106.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987 Sep 4;237(4819):1154–1162. doi: 10.1126/science.3306916. [DOI] [PubMed] [Google Scholar]
  24. Lieberburg I. Developmental expression and regional distribution of the scrapie-associated protein mRNA in the rat central nervous system. Brain Res. 1987 Aug 11;417(2):363–366. doi: 10.1016/0006-8993(87)90465-3. [DOI] [PubMed] [Google Scholar]
  25. Masiakowski P., Shooter E. M. Nerve growth factor induces the genes for two proteins related to a family of calcium-binding proteins in PC12 cells. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1277–1281. doi: 10.1073/pnas.85.4.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. doi: 10.1073/pnas.82.12.4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. McKinley M. P., Hay B., Lingappa V. R., Lieberburg I., Prusiner S. B. Developmental expression of prion protein gene in brain. Dev Biol. 1987 May;121(1):105–110. doi: 10.1016/0012-1606(87)90143-6. [DOI] [PubMed] [Google Scholar]
  28. Mesulam M. M., Mufson E. J., Wainer B. H., Levey A. I. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience. 1983 Dec;10(4):1185–1201. doi: 10.1016/0306-4522(83)90108-2. [DOI] [PubMed] [Google Scholar]
  29. Meyer R. K., McKinley M. P., Bowman K. A., Braunfeld M. B., Barry R. A., Prusiner S. B. Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2310–2314. doi: 10.1073/pnas.83.8.2310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Milner T. A., Loy R., Amaral D. G. An anatomical study of the development of the septo-hippocampal projection in the rat. Brain Res. 1983 Jun;284(2-3):343–371. doi: 10.1016/0165-3806(83)90017-2. [DOI] [PubMed] [Google Scholar]
  31. Mobley W. C., Rutkowski J. L., Tennekoon G. I., Buchanan K., Johnston M. V. Choline acetyltransferase activity in striatum of neonatal rats increased by nerve growth factor. Science. 1985 Jul 19;229(4710):284–287. doi: 10.1126/science.2861660. [DOI] [PubMed] [Google Scholar]
  32. Mobley W. C., Rutkowski J. L., Tennekoon G. I., Gemski J., Buchanan K., Johnston M. V. Nerve growth factor increases choline acetyltransferase activity in developing basal forebrain neurons. Brain Res. 1986 Jul;387(1):53–62. doi: 10.1016/0169-328x(86)90020-3. [DOI] [PubMed] [Google Scholar]
  33. Oesch B., Westaway D., Wälchli M., McKinley M. P., Kent S. B., Aebersold R., Barry R. A., Tempst P., Teplow D. B., Hood L. E. A cellular gene encodes scrapie PrP 27-30 protein. Cell. 1985 Apr;40(4):735–746. doi: 10.1016/0092-8674(85)90333-2. [DOI] [PubMed] [Google Scholar]
  34. Ponte P., Gonzalez-DeWhitt P., Schilling J., Miller J., Hsu D., Greenberg B., Davis K., Wallace W., Lieberburg I., Fuller F. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature. 1988 Feb 11;331(6156):525–527. doi: 10.1038/331525a0. [DOI] [PubMed] [Google Scholar]
  35. Prusiner S. B. Prions and neurodegenerative diseases. N Engl J Med. 1987 Dec 17;317(25):1571–1581. doi: 10.1056/NEJM198712173172505. [DOI] [PubMed] [Google Scholar]
  36. Richardson P. M., Issa V. M., Riopelle R. J. Distribution of neuronal receptors for nerve growth factor in the rat. J Neurosci. 1986 Aug;6(8):2312–2321. doi: 10.1523/JNEUROSCI.06-08-02312.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Roberts G. W., Lofthouse R., Allsop D., Landon M., Kidd M., Prusiner S. B., Crow T. J. CNS amyloid proteins in neurodegenerative diseases. Neurology. 1988 Oct;38(10):1534–1540. doi: 10.1212/wnl.38.10.1534. [DOI] [PubMed] [Google Scholar]
  38. Schubert D., Schroeder R., LaCorbiere M., Saitoh T., Cole G. Amyloid beta protein precursor is possibly a heparan sulfate proteoglycan core protein. Science. 1988 Jul 8;241(4862):223–226. doi: 10.1126/science.2968652. [DOI] [PubMed] [Google Scholar]
  39. Shank P. R., Hughes S. H., Kung H. J., Majors J. E., Quintrell N., Guntaka R. V., Bishop J. M., Varmus H. E. Mapping unintegrated avian sarcoma virus DNA: termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA. Cell. 1978 Dec;15(4):1383–1395. doi: 10.1016/0092-8674(78)90063-6. [DOI] [PubMed] [Google Scholar]
  40. Shelton D. L., Nadler J. V., Cotman C. W. Development of high affinity choline uptake and associated acetylcholine synthesis in the rat fascia dentata. Brain Res. 1979 Mar 16;163(2):263–275. doi: 10.1016/0006-8993(79)90354-8. [DOI] [PubMed] [Google Scholar]
  41. Shivers B. D., Hilbich C., Multhaup G., Salbaum M., Beyreuther K., Seeburg P. H. Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO J. 1988 May;7(5):1365–1370. doi: 10.1002/j.1460-2075.1988.tb02952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Stahl N., Borchelt D. R., Hsiao K., Prusiner S. B. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell. 1987 Oct 23;51(2):229–240. doi: 10.1016/0092-8674(87)90150-4. [DOI] [PubMed] [Google Scholar]
  43. Tanzi R. E., Gusella J. F., Watkins P. C., Bruns G. A., St George-Hyslop P., Van Keuren M. L., Patterson D., Pagan S., Kurnit D. M., Neve R. L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science. 1987 Feb 20;235(4791):880–884. doi: 10.1126/science.2949367. [DOI] [PubMed] [Google Scholar]
  44. Tanzi R. E., McClatchey A. I., Lamperti E. D., Villa-Komaroff L., Gusella J. F., Neve R. L. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature. 1988 Feb 11;331(6156):528–530. doi: 10.1038/331528a0. [DOI] [PubMed] [Google Scholar]
  45. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tiercy J. M., Shooter E. M. Early changes in the synthesis of nuclear and cytoplasmic proteins are induced by nerve growth factor in differentiating rat PC12 cells. J Cell Biol. 1986 Dec;103(6 Pt 1):2367–2378. doi: 10.1083/jcb.103.6.2367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Whittemore S. R., Seiger A. The expression, localization and functional significance of beta-nerve growth factor in the central nervous system. Brain Res. 1987 Nov;434(4):439–464. doi: 10.1016/0165-0173(87)90008-7. [DOI] [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