Skip to main content
Log in

5-HT1A Receptor Agonist Reverses Adrenalectomy-Induced Loss of Granule Neuronal Morphology in the Rat Dentate Gyrus

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Adrenal steroids are important for maintaining neuronal maturation in the adult rats. Two weeks after bilateral adrenalectomy (ADX), hippocampal MAP-2 (microtubule associated protein-2) and calbindin immunoreactivity (IR) decreased in the molecular layer of the superior blade of the dentate gyrus. The molecular and granular cell layer at the lateral tip of the superior blade decreased in width by 32% and 50%, respectively. The granule neurons showed reduced staining with Nissl and an anti-calbindin antibody. These changes suggested a loss of the mature neuronal morphology. In this same localized regions, two glial proteins, glial fibrillary acidic protein (GFAP) and S-100β showed dramatically reduced immunoreactivity. These effects induced by ADX were reduced within 72 hrs by ipsapirone (1 mg/kg), a 5HT1A receptor agonist. Loss of adult neuronal morphology by ADX, and reversal by the 5HT1A agonist, may be evidence of the trophic importance of the 5HT1A receptor in granule neurons of hippocampus.

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.

Similar content being viewed by others

REFERENCES

  1. Altman, J., and S. A. Bayer. 1975. Postnatal development of the hippocampal dentate gyrus under normal and experiment conditions. Pages 95–122, in R. L. Isaacson and K. H. Pribram, (eds) The Hippocampus Vol. 1; Plenum Press. New York.

    Google Scholar 

  2. Azmitia, E. C., and B. S. McEwen. 1969 Corticosterone regulation of tryptophan hydroxylase in midbrain of the rat. Science. 166: 1274–1276.

    Google Scholar 

  3. Azmitia, E. C., S. Algeri, and E. Costa. 1970. In vivo conversion of 3H-serotonin in brain areas of adrenalectomized rats. Science. 169:201–203.

    Google Scholar 

  4. Azmitia, E. C. 1973. Rapid alteration in rat brain tryptophan hydroxylase activity; effect of adrenal steroids, drugs and stressor. Ph. D. dissertation. The Rockfeller University. New York.

    Google Scholar 

  5. Azmitia, E. C., V. J. Rubinstein, J. A. Strafaci, J. C. Rios, and P. M. Whitaker-Azmitia. 1995. 5HT1A agonist and dexamethasone reversal of para-chloroamphetamine induced loss of MAP-2 and synaptophysin immunoreactivity in adult rat brain. Brain Res. 677: 181–192.

    Google Scholar 

  6. Azmitia E. C., and B. Liao 1994. Dexamethasone reverses adrenalectomy-induced neuronal de-differentiation in midbrain raphe-hippocampus axis. The Annals of the New York Academy of Sciences 746:180–194.

    Google Scholar 

  7. Azmitia E. C., B. Liao, and Y. Chen 1993. Increase of tryptophan hydroxylase enzyme protein by dexamethasone in adrenalectomized rat midbrain. J. Neurosci. 13(12):5041–5055.

    Google Scholar 

  8. Azmitia, E. C., W. S. T. Griffin, D. R. Marshak, L. J. Van Eldik, and P. M. Whitaker-Azmitia. 1992. S-100β and serotonin: a possible astrocytic-neuronal link to neuropathology of Alzheimer's disease. Prog. Brain Res. 94:459–473.

    Google Scholar 

  9. Boadle-Biber, M. C., K. C. Corley, L Graves, T. Phan, and J. Rosecrans. 1989. Increase in the activity of tryptophan hydroxylase from cortex and midbrain of male Fischer 344 rats in response to acute or repeated sound stress. Brain Res. 482:306–316.

    Google Scholar 

  10. Bohn, M. C. 1979. Effects of hydrocortisone on neurogenesis in the neonatal rat brain: a morphological and autoradiographic study. Ph.D. dissertation. University of Connecticut at Storrs.

  11. Chalmers, D. T., Kwak, S. P., Mansour, A., Akil, H., and Watson, S. J. 1993. Corticosteroids regulate brain hippocampal 5-HT-1A receptor mRNA expression, J. Neurosci., 13:914–923.

    Google Scholar 

  12. Cheng, L., Hamaguchi, K., Ogawa, M., Hamada, S., and Okado, N. 1994. PCPA reduces both monoaminergic afferents and non-monoaminergic synapses in the cerebral cortex, Neurosci. Res., 19:111–115.

    Google Scholar 

  13. Daval G., Verge D., Becerril A., Gozlan H. Sampinato U., and Hamon M. 1987. Transient expression of 5HT1A receptor binding sites in some areas of rat CNS during postnatal development. Int. J. Dev. Neuroscience. 5:171–180.

    Google Scholar 

  14. De Kloet, E. R., G. L. Kovacs, G. Szabo, G. Telegdy, B. Bohus, and D. H. G. Versteeg. 1982. Decreased serotonin turnover in the dorsal hippocampus of rat brain shortly after adrenalectomy: selective normalization after corticosterone substitution. Brain Res. 239:659–663.

    Google Scholar 

  15. Dedeoglu A., and Fisher LA. 1994. Cardiovascular activation by serotonergic stimulation: role of corticotrophin-releasing factor. American Journal of Physiology. 267(3 pt 2):R859–64.

    Google Scholar 

  16. Gould, H., C. S. Woolley, and B. S. McEwen. 1990. Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus. Neuroscience 37:367–375.

    Google Scholar 

  17. Hellendall, R. P., U. Schambra, J. Liu, G. R. Bresse, D. E. Millhorn, and J. Lauder. 1992. Detection of serotonin receptor transcripts in the developing nervous system. J. Chem. Neuroant. 5: 2799–310.

    Google Scholar 

  18. Krugers H. J., Medema R. M., Postema F., and Korf J. 1994. Induction of glial fibrillary acidic protein immunoreactivity in the rat dentate gyrus after adrenalectomy: comparison with neurodegenerative changes using silver impregnation. Hippocampus. 4(3): 307–14.

    Google Scholar 

  19. Lauder, J., and Krebs, H. 1978. Serotonin as a differentiation signal in early neurogenesis. Dev. Neurosci., 1:15–30.

    Google Scholar 

  20. Lauder, J. M. 1990. Ontogeny of the serotonergic system in the rat: serotonin as a development signal. Ann NY Acad. Sci 600: 297–308.

    Google Scholar 

  21. Liao, B., Mieska, B., and Azmitia, E. C., 1993. Loss of 5-HT1A receptor mRNA in the dentate gyrus of the long-term adrenalectomized rats and rapid reversal by dexamethasone. Mol. Brain Res., 19:328–332.

    Google Scholar 

  22. Liao, B. 1995. Differential effects of corticosteroids on neuronal and glial cells in the adult rat hippocampus. PH.D. dissertation. Department of Biology, New York University, New York.

    Google Scholar 

  23. Meller, E., and Bohmaker, K. 1994. Differential receptor reserve for 5-HT1A receptor-mediated regulation of plasma neuroendocrine hormones. Journal of Pharmacology & Experimental Therapeutics. 271(3): 1246–52.

    Google Scholar 

  24. Nichols, N. R., Osterburg, H. H., Masters, J. N., Millar, S. L., and Finch, C. E. 1990. Messenger RNA for glial fibrillary acidic protein is decreased in rat brain following acute or chronic corticosterone treatment. Mol. Brain Res., 7:1–7.

    Google Scholar 

  25. Nishi, M., Whitaker-Azmitia, P. M., and Azmitia, E. C. 1996. Effects of 5HT1A agonist and S-100β and steroids on synaptophysin immunoreactivity in cultured hippocampal neurons. Synapse. 23:1–9.

    Google Scholar 

  26. Sloviter, R. S., G. Valiquette, G. M. Abrams, E. C. Ronk, A. L. Sollas, L. A. Paul, and S. Neubort. 1989. Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science 243:535–538.

    Google Scholar 

  27. Whitaker-Azmitia P. M., and Azmitia E. C. 1986. 5-hydroxytryptamine binding to brain astroglial cells: difference between intact and homogenized preparations and mature and immature cultures. J. Neurochem. 46:1186–9.

    Google Scholar 

  28. Whitaker-Azmitia, P. M., R. Murphy, and E. C. Azmitia. 1990. Stimulation of astroglial 5HT1A receptor releases the serotonergic growth factor, protein S-100β, and alters astroglial morphology. Brain Res. 528:155–158.

    Google Scholar 

  29. Woolley, C. S., E. Gould, R. R. Sakai, R. L. Spencer, and B. S. McEwen. 1991. Effects of aldosterone or RU28362 treatment on adrenalectomy-induced cell death in the dentate gyrus of the adult rat. Brain Res. 554:312–315.

    Google Scholar 

  30. Zifa, E., and Fillion, G. 1992. 5-Hydroxytryptamine receptors. Pharmacological Reviews. 44(3)401–458.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, J., Strafaci, J.A. & Azmitia, E.C. 5-HT1A Receptor Agonist Reverses Adrenalectomy-Induced Loss of Granule Neuronal Morphology in the Rat Dentate Gyrus. Neurochem Res 22, 1329–1337 (1997). https://doi.org/10.1023/A:1022062921438

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022062921438

Navigation