Skip to main content

Advertisement

SpringerLink
Log in

Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

Alzheimer's disease is a progressive degenerative disease of the nervous system characterized neuropathologically by the presence of senile plaques and neurofibrillary tangles in amygdala, hippocampus and neocortex1–4. Dysfunction and death of basal forebrain cholinergic neurones projecting to forebrain targets5,6 are associated with marked decreases in cholinergic markers, including the activity of choline acetyltransferase (ChAT)2,3,7–9. Although cortical levels of somatostatin10–12 and somatostatin receptors13 are reduced in Alzheimer’s, no consistent changes have been reported in other neuropeptide systems12,14–17. We have now examined in control and Alzheimer’s brain tissues pre- and postsynaptic markers of corticotropin-releasing factor (CRF), a hypothalamic peptide regulating pituitary-adrenocortical secretion18,19 which also seems to act as a neu retransmitter in the central nervous system (CNS) (reviewed in refs 20, 21). We have found that in Alzheimer’s, the concentrations of CRF-like immunoreactivity (CRF-IR) are reduced and that there are reciprocal increases in CRF receptor binding in affected cortical areas. These changes are significantly correlated with decrements in ChAT activity. Our results strongly support a neurotransmitter role for CRF in brain and demonstrate, for the first time, a modulation of CNS CRF receptors associated with altered CRF content. These observations further suggest a possible role for CRF in the pathophysiology of the dementia. Future therapies directed at increasing CRF levels in brain may prove useful for treatment.

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

Access this article

Log in via an institution

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. Terry, R. D. & Davies, P. A. Rev. Neurosci. 3, 77–95 (1980).

    Article  CAS  Google Scholar 

  2. Price, D. L., Whitehouse, P. J. & Struble, R. G. A. Rev. Med. 36, 349–356 (1985).

    Article  CAS  Google Scholar 

  3. Bowen, D. M., Smith, C. B., White, P. & Davison, A. N. Brain 99, 459–496 (1976).

    Article  CAS  Google Scholar 

  4. Terry, R. D. & Katzman, R. Ann. Neurol. 14, 497–506 (1983).

    Article  CAS  Google Scholar 

  5. Whitehouse, P. J. et al. Science 215, 1237–1239 (1982).

    Article  ADS  CAS  Google Scholar 

  6. Cuello, A. C. & Sofroniew, M. V. Trends Neurosci. 7, 74–78 (1984).

    Article  CAS  Google Scholar 

  7. Davies, P. & Maloney, A. J. R. Lancet ii, 1403 (1976).

    Article  Google Scholar 

  8. Perry, E. K., Perry, R. H., Blessed, G. & Tomlinson, B. E. Lancet i, 89 (1977).

    Google Scholar 

  9. Rossor, M. N., Iversen, L. L., Reynolds, G. P., Mountjoy, C. Q. & Roth, M. Br. med. J. 288, 961 (1984).

    Article  CAS  Google Scholar 

  10. Davies, P., Katzman, R. & Terry, R. D. Nature 288, 279–280 (1980).

    Article  ADS  CAS  Google Scholar 

  11. Rossor, M., Emson, P. C., Mountjoy, C. G., Roth, S. M. & Iversen, L. L. Neurosci Lett. 20, 373–377 (1980).

    Article  CAS  Google Scholar 

  12. Ferrier, I. N. et al. J. neurol. Sci. 62, 159–170 (1983).

    Article  CAS  Google Scholar 

  13. Beal, M. F. et al. Science 229, 289–291 (1985).

    Article  ADS  CAS  Google Scholar 

  14. Rossor, M. N. et al. Life Sci. 29, 405–410 (1981).

    Article  CAS  Google Scholar 

  15. Rossor, M. N. et al. Brain Res. 201, 249–253 (1980).

    Article  CAS  Google Scholar 

  16. Yates, C. M. et al. Brain Res. 258, 45–52 (1983).

    Article  CAS  Google Scholar 

  17. Biggins, J. A. et al. J. neurol. Sci. 58, 117–122 (1983).

    Article  CAS  Google Scholar 

  18. Vale, W., Spiess, J., Rivier, C. & Rivier, J. Science 213, 1394–1397 (1981).

    Article  ADS  CAS  Google Scholar 

  19. Rivier, C., Rivier, J. & Vale, W. W. Science 218, 377–379 (1982).

    Article  ADS  CAS  Google Scholar 

  20. Vale, W. et al. Recent Prog. Horm. Res. 39, 245–270 (1983).

    CAS  PubMed  Google Scholar 

  21. De Souza, E. B. Compreh. Ther. 11, 3–5 (1985).

    CAS  Google Scholar 

  22. Vale, W. et al. Meth. Enzym. 103, 565–577 (1983).

    Article  CAS  Google Scholar 

  23. Bull, G. & Oderfeld-Nowak, B. J. Neurochem. 18, 935–94 (1971).

    Article  CAS  Google Scholar 

  24. De Souza, E. B., Perrin, M. H., Rivier, J. E., Vale, W. W. & Kuhar, M. J. Brain Res. 296, 202–207 (1984).

    Article  CAS  Google Scholar 

  25. De Souza, E. B. et al. Neuroendocrinology 40, 419–422 (1985).

    Article  CAS  Google Scholar 

  26. De Souza, E. B. et al. Science 224, 1449–1451 (1984).

    Article  ADS  CAS  Google Scholar 

  27. De Souza, E. B. et al. J. Neurosci. 5, 3189–3202 (1985).

    Article  CAS  Google Scholar 

  28. Wynn, P. C., Aguilera, G., Morell, J. & Catt, K. J. Biochem. biophys. Res. Commun. 110, 602–608 (1983).

    Article  CAS  Google Scholar 

  29. Wynn, P. C. et al. Peptides 5, 1077–1084 (1984).

    Article  CAS  Google Scholar 

  30. Olschowka, J. A., O'Donohue, T. L., Mueller, G. P. & Jacobowitz, D. M. Peptides 3, 995–1015 (1982).

    Article  CAS  Google Scholar 

  31. Swanson, L. W., Sawchenko, P. E., Rivier, J. & Vale, W.W. Neuroendocrinology 36, 165–186 (1983).

    Article  CAS  Google Scholar 

  32. Bissette, G., Reynolds, G. P., Kilts, C. D., Widerlov, E. & Nemeroff, C. B. J. Am. med. Ass. 254, 3067–3069 (1985).

    Article  CAS  Google Scholar 

  33. Jacobowitz, D. M., Skofitsch, G., Sills, M. A. & Crawley, J. N. Neural and Endocrine Peptides and Receptors '85, abstr., 39 (1985).

  34. Whitehouse, P. J. & Au, K. S. Prog. Neuropsychopharmacol Biol. Psychiat. (in the press).

  35. Lang, W. & Henke, H. Brain Res. 267, 271–280 (1983).

    Article  CAS  Google Scholar 

  36. Mash, D. C., Flynn, D. D. & Potter, L. T. Science 228, 1115–1117 (1985).

    Article  ADS  CAS  Google Scholar 

  37. Bird, T. D., Stranahan, S., Sumi, S. M. & Raskind, M. Ann. Neurol. 14, 284–293 (1983).

    Article  CAS  Google Scholar 

  38. Sims, N. R. et al. J. Neurochem. 40, 503–509 (1983).

    Article  CAS  Google Scholar 

  39. Crawley, J. N., Olschowska, J. A., Diz, D. & Jacobowitz, D. Peptides 6, 891–901 (1985).

    Article  CAS  Google Scholar 

  40. Peterfreund, R. A. & Vale, W. W. Endocrinology 112, 1275–1278 (1983).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland, 21224, USA

    Errol B. De Souza & Michael J. Kuhar

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Errol B. De Souza, Peter J. Whitehouse, Michael J. Kuhar & Donald L. Price

  3. Neuropathology Laboratory, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Peter J. Whitehouse & Donald L. Price

  4. Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California, 92037, USA

    Wylie W. Vale

Authors
  1. Errol B. De Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J. Whitehouse
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. Kuhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Donald L. Price
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wylie W. Vale
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Souza, E., Whitehouse, P., Kuhar, M. et al. Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease. Nature 319, 593–595 (1986). https://doi.org/10.1038/319593a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/319593a0

  • Springer Nature Limited

This article is cited by

Search

Navigation