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Corticosterone replacement restores normal morphological features to the hippocampal dendrites, axons and synapses of adrenalectomized rats

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Journal of Neurocytology

Abstract

A thorough evaluation of hippocampal dendrites, axons and synaptic contacts has not been undertaken following prolonged periods of absence of corticosteroids despite the marked granule cell loss which occurs in the dentate gyrus of adrenalectomized rats. Thus, we have applied morphometric techniques to analyse the dendrites of granule and pyramidal cells, the mossy fiber system, and the number and morphology of synapses between the mossy fibers and the excrescences of CA3 pyramidal cells in rats submitted to different periods of adrenalectomy. In addition, to search for the presence of neuritic reorganisation in the hippocampal formation once normal corticosteroid levels were re-established, we incorporated in this study a group of rats replaced with corticosterone one month after adrenalectomy. The results obtained in adrenalectomized rats showed a striking impoverishment of the dendrites of surviving granule cells, subtle alterations in the apical dendritic arborization of CA3 pyramidal cells and no changes in the apical dendrites of CA1 pyramidal cells. In addition, in adrenalectomized rats there was a progressive reduction in the total number of synapses established between mossy fibers and CA3 pyramids, as a consequence of a reduction in the volume of the suprapyramidal part of the mossy fiber system, and profound changes in the morphology of mossy fiber terminals and CA3 dendritic excrescences. A remarkable reorganisation of neurites was found to occur following the administration of low doses of corticosterone, completely reversing the adrenalectomy-induced synaptic loss and partially restoring the morphology of hippocampal axons and dendrites. These plastic mechanisms provide a sound structural basis for the reversibility of cognitive deficits observed after corticosterone administration to adrenalectomized rats.

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References

  • Adem, A., Islam, A., Bogdanovic, N., Carlstrom, K. & Winblad, B. (1994) Loss of neurones after long-term adrenalectomy in the adult rat hippocampal formation. NeuroReport 5, 2285–2288.

    Google Scholar 

  • Altman, J. & Bayer, S. A. (1990) Migration and distribution of two populations of hippocampal granule cell precursors. Journal of Comparative Neurology 301, 365–381.

    Google Scholar 

  • Amaral, D. G. & Dent, J. A. (1981) Development of the mossy fibers of the dentate gyrus: I. A light and electron microscopic study of the mossy fibers and their expansions. Journal of Comparative Neurology 195, 51–86.

    Google Scholar 

  • Amaral, D. G. & Witter, M. P. (1989) The threedimensional organization of the hippocampal formation: A review of anatomical data. Neuroscience 31, 571–591.

    Google Scholar 

  • Andrade, J. P., Madeira, M. D. & Paulabarbosa, M. M. (1995) Evidence of reorganization in the hippocampal mossy fiber synapses of adult rats rehabilitated after prolonged undernutrition. Experimental Brain Research 104, 249–261.

    Google Scholar 

  • Andrade, J. P., Castanheira-vale, A. J., Pazdias, P. G., Madeira, M. D. & Paula-barbosa, M. M. (1996) The dendritic trees of neurons from the hippocampal formation of protein-deprived adult rats. A quantitative Golgi study. Experimental Brain Research 109, 419–433.

    Google Scholar 

  • Armstrong, J. N., Mc Intyre, D. C., Neubort, S. & Sloviter, R. S. (1993) Learning and memory after adrenalectomy-induced hippocampal dentate granule cell degeneration in the rat. Hippocampus 3, 359–371.

    Google Scholar 

  • Baddeley, A. J., Gundersen, H. J. G. & Cruzorive, L. M. (1986) Estimation of surface area from vertical sections. Journal of Microscopy 142, 259–276.

    Google Scholar 

  • Barbany, G. & Persson, H. (1993) Adrenalectomy attenuates kainic acid-elicited increases of messenger RNAs for neurotrophins and their receptors in the rat brain. Neuroscience 54, 909–922.

    Google Scholar 

  • Ben-ari, Y. & Represa, A. (1990) Brief seizure episodes induce long-term potentiation and mossy fiber sprouting in the hippocampus. Trends in Neuroscience 13, 312–318.

    Google Scholar 

  • Cadete-leite, A., Tavares, M. A., Pacheco, M. M., Volk, B. & Paula-barbosa, M. M. (1989) Hippocampal mossy fiber-CA3 synapses after chronic alcohol consumption and withdrawal. Alcohol 6, 303–310.

    Google Scholar 

  • Cameron, H. A. & Gould, E. (1996) Distinct populations of cells in the adult dentate gyrus undergo mitosis or apoptosis in response to adrenalectomy. Journal of Comparative Neurology 369, 56–63.

    Google Scholar 

  • Collazo, D., Takahashi, H. & Mc Ray, R. D. G. (1992) Cellular targets and trophic functions of neurotrophin-3 in the developing hippocampus. Neuron 9, 643–656.

    Google Scholar 

  • Conrad, C. D. & Roy, E. J. (1993) Selective loss of hippocampal granule cells following adrenalectomy: Implications for spatial memory. Journal of Neuroscience 13, 2582–2590.

    Google Scholar 

  • Conrad, C. D. & Roy, E. J. (1995) Dentate gyrus destruction and spatial learning impairment after corticosteroid removal in young and middle-aged rats. Hippocampus 5, 1–15.

    Google Scholar 

  • Danscher, G. & Zimmer, J. (1978) An improved Timm sulphide silver method for light and electron microscopic localization of heavy metals in biological tissues. Histochemistry 55, 27–40.

    Google Scholar 

  • De ruiter, J. P. & Uylings, H. B. M. (1987) Morphometric and dendritic analysis of fascia dentata granule cells in human aging and senile dementia. Brain Research 402, 217–229.

    Google Scholar 

  • De Voogt, T. J., Chang, F. L. F., Floeter, M. K., Jencius, M. J. & Greenough, W. T. (1981) Distortions induced in neuronal quantification by camera lucida analysis: Comparisons with a semi-automated data acquisition system. Journal of Neuroscience Methods 3, 285–294.

    Google Scholar 

  • Denton, T. L., Dugich-djordjevic, M. N., Nichols, N. R., Davenport, C. J., Finch, C. E. & Hefti, F. (1992) Changes in the expression of the neurotrophins BDNF and NT3 may mediate the dependence of hippocampal neurons on glucocorticoid levels. Society for Neuroscience Abstracts 18, A387.5.

    Google Scholar 

  • Desmond, N. L. & Levy, W. B. (1986) Changes in the numerical density of synaptic contacts with long-term potentiation in the hippocampal dentate gyrus. Journal of Comparative Neurology 253, 466–475.

    Google Scholar 

  • Eayrs, T. J. (1955) The cerebral cortex of normal and hypothyroid rats. Acta Anatomica 25, 160–183.

    Google Scholar 

  • Eckenhoff, M. F. & Rakic, P. (1984) Radial organization of the hippocampal dentate gyrus: A Golgi, ultrastructural and immunocytochemical analysis in the developing Rhesus monkey. Journal of Comparative Neurology 223, 1–21.

    Google Scholar 

  • Eichenbaum, H., Otto, T. & Cohen, N. J. (1992) The hippocampus: What does it do? Behavioural Neural Biology 57, 2–36.

    Google Scholar 

  • Elshamy, W. M. & Enfors, P. (1996) A local action of neurotrophin-3 prevents the death of proliferation sensory neuron precursor cells. Neuron 16, 963–972.

    Google Scholar 

  • Freidman, W. J., Enfors, P. & Persson, H. (1991) Transient and persistent expression of NT-3/3DNF mRNA in the rat brain during postnatal development. Journal of Neuroscience 11, 1577–1584.

    Google Scholar 

  • Gaarskjaer, F. B. (1978) Organization of the mossy fiber system of the rat studied in extended hippocampi. I. Terminal area related to number of granule and pyramidal cells. Journal of Comparative Neurology 178, 49–72.

    Google Scholar 

  • Gould, E., Woolley, C. S. & Mc Ewen, B. S. (1990) Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus. Neuroscience 37, 367–375.

    Google Scholar 

  • Gundersen, H. J. G. & Jensen, E. B. (1987) The efficacy of systematic sampling in stereology and its prediction. Journal of Microscopy 147, 229–263.

    Google Scholar 

  • Hoff, S. F. (1986) Lesion-induced transneuronal plasticity in the adult rat hippocampus. Neuroscience 19, 1227–1233.

    Google Scholar 

  • Hornsby, C. D., Grootendorst, J. & De Kloet, E. R. (1996) Dexamethasone does not prevent seven-day ADX-induced apoptosis in the dentate gyrus of the rat hippocampus. Stress 1, 51–64.

    Google Scholar 

  • Hu, Z., Yuri, K., Ozawa, H., Lu, H. & Kawata, M. (1997) The in vivo time course for elimination of adrenalectomy-induced apoptotic profiles fromthe granule cell layer of the rat hippocampus. Journal of Neuroscience 17, 3981–3989.

    Google Scholar 

  • Islam, A., Henrikson, B., Mohammed, A., Winblad, B. & Adem, A. (1995) Behavioural deficits following long-term adrenalectomy. Neuroscience Letters 194, 49–52.

    Google Scholar 

  • Jaarsma, D., Postema, F. & Korf, J. (1992) Time course and distribution of neuronal degeneration in the dentate gyrus of rat after adrenalectomy: A silver impregnation study. Hippocampus 2, 143–150.

    Google Scholar 

  • Jensen, E. B. & Gundersen, H. J. G. (1982) Stereological ratio estimated based on counts from integral tests systems. Journal of Microscopy 125, 51–66.

    Google Scholar 

  • Krugers, H. J., Medema, R. M., Postema, F. & Korf, J. (1995) Region-specific alterations of calbidin-D28k immunoreactivity in the rat hippocampus following adrenalectomy and corticosterone treatment. Brain Research 696, 89–96.

    Google Scholar 

  • Landfield, P. W., Baskin, R. K. & Pitler, T. A. (1981) Brain aging correlates: Retardation by hormonalpharmacological treatments. Science 214, 581–584.

    Google Scholar 

  • Laurberg, S. & Zimmer, J. (1980) Lesion-induced sprouting of hippocampal mossy fibers in developing but not in adult rats. Journal of Comparative Neurology 190, 627–650.

    Google Scholar 

  • Lorente De Nó, R. (1934) Studies on the structure of cerebral cortex. II. Continuation of the study of ammonic system. Journal of Psychology and Neurology 46, 113–117.

    Google Scholar 

  • Maclennan, K. M., Smith, P. F. & Darlington, C. L. (1998) Adrenalectomy-induced neuronal degeneration. Progress in Neurobiology 54, 481–498.

    Google Scholar 

  • Madeira, M. D. & Paula-barbosa, M. M. (1993) Reorganization of mossy fiber synapses in male and female hypothyroid rats: A stereological study. Journal of Comparative Neurology 337, 334–352.

    Google Scholar 

  • Mayhew, T. M. (1992) Areview of recent advances in stereology for quantifying neural structure. Journal of Neurocytology 21, 313–328.

    Google Scholar 

  • Mayhew, T. M. & Gundersen H. J. G. (1996) ÒIf you assume, you can make an ass out of u and meÓ a decade of the disector for stereological counting of particles in 3D space. Journal of Anatomy 188, 1–15.

    Google Scholar 

  • Mc Cormick, C. M., Mcnamara, M., Mukhopadhyay, S. & Kelsey, J. E. (1997) Acute corticosterone replacement reinstates performance on spatial and nonspatial memory tasks 3 months after adrenalectomy despite degeneration in the dentate gyrus. Behavioural Neuroscience 111, 518–531.

    Google Scholar 

  • Mc Ewen, B. S., De Kloet, E. R. & Rostene, W. (1986) Adrenal steroids receptors and actions in the nervous system. Physiological Reviews 66, 1121–1188.

    Google Scholar 

  • Mc Neill, T. H., Masters, J. N. & Finch, C. E. (1991) Effect of chronic adrenalectomy on neuron loss and distribution of sulphated glycoprotein-2 in the dentate gyrus of prepubertal rats. Experimental Neurology 111, 140–144.

    Google Scholar 

  • Moore, D. S. & Mc Cabe, G. P. (1989) Introduction to the Practice of Statistics. New York: Freeman.

    Google Scholar 

  • Palay, S. L. & Chan-palay, V. (1974) Cerebellar Cortex. Cytology and Organisation. pp. 332–336. Berlin: Springer.

    Google Scholar 

  • Popov, V. I. & Bocharova, L. S. (1992) Hibernationinduced structural changes in synaptic contacts between mossy fibers and hippocampal pyramidal neurons. Neuroscience 48, 53–82.

    Google Scholar 

  • Qiao, X., Hughes, P. E., Venero, J. L., Dugichdjordjevic, M. M., Nichols, N. R., Hefti, F. & Knusel, B. (1996) NT-4/5 protects against adrenalectomy-induced apoptosis of rat hippocampal granule cells. NeuroReport 7, 682–686.

    Google Scholar 

  • Ravindran, J., Shuaib, A., Ijaz, S., Galazka, P., Waqar, T., Ishaqzay, R., Miyashita, H. & Liu, L. (1994) High extracellular GABA levels in hippocampusÑAs a mechanism of neuronal protection in cerebral ischemia in adrenalectomized gerbils. Neuroscience Letters 176, 209–211.

    Google Scholar 

  • Reul, J. M. H. M. & De Kloet, E. R. (1985) Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation. Endocrinology 117, 2505–2511.

    Google Scholar 

  • Roy, E. J., Lynn, D. M. & Bemm, C. W. (1990) Individual variations in hippocampal dentate degeneration following adrenalectomy. Behavioural Neural Biology 54, 330–336.

    Google Scholar 

  • Sakhi, S., Gilmore, W., Tran, N. D. & Schreiber, S. S. (1996) p53 deficient mice are protected against adrenalectomy-induced apoptosis. NeuroReport 8, 233–235.

    Google Scholar 

  • Sapolsky, R. M., Stein-behrens, B. A. & Armanini, M. P. (1991) Long-term adrenalectomy causes loss of dentate gyrus and pyramidal neurons in the adult hippocampus. Experimental Neurology 114, 246–249.

    Google Scholar 

  • Schreiber, S. S., Sakhi, S., Dugich-djordjevic, M. M. & Nichols, N. R. (1994) Tumor suppressor p53 induction and DNA damage in hippocampal granule cells after adrenalectomy. Experimental Neurology 130, 368–476.

    Google Scholar 

  • Schuz, A. & Palm, G. (1989) Density of neurons and synapses in the cerebral cortex of the mouse. Journal of Comparative Neurology 286, 442–455.

    Google Scholar 

  • Sloviter, R. S. (1989) Calcium-binding protein (calbindin-D28k) and parvalbumin immunocytochemistry: Localization in the rat hippocampus with specific reference to the selective vulnerability of hippocampal neurons to seizure activity. Journal of Comparative Neurology 280, 183–196.

    Google Scholar 

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

    Google Scholar 

  • Sloviter, R. S., Dean, E. & Neubort, S. (1993a) Electron microscopic analysis of adrenalectomy-induced hippocampal granule cell degeneration in the rat: Apoptosis in the adult central nervous system. Journal of Comparative Neurology 330, 337–351.

    Google Scholar 

  • Sloviter, R. S., Sollas, A. L., Dean, E. & Neubort, S. (1993b) Adrenalectomy-induced granule cell degeneration in the rat hippocampal dentate gyrus: Characterization of an in vivomodel of controlled neuronal death. Journal of Comparative Neurology 330, 324–336.

    Google Scholar 

  • Sloviter, R. S., Sollas, A. L. & Neubort, S. (1995) Hippocampal dentate granule cell degeneration after adrenalectomy in the rat is not reversed by dexamethasone. Brain Research 682, 227–230.

    Google Scholar 

  • Small, J. V. (1968) Measurements of section thickness. In Proceedings of the 4th European Congress of Electron Microscopy(edited by Bocciarelli, D. S.), p. 609. Rome: Tipografia Poliglotta Vaticana.

    Google Scholar 

  • Smith, M. A., Makino, S., Kvetnansky, R. & Post, R. M. (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. Journal of Neuroscience 15, 1768–1777.

    Google Scholar 

  • Sousa, N., Madeira, M. D. & Paula-barbosa, M. M. (1997) Structural alterations of the hippocampal formation of adrenalectomized rats: An unbiased stereological study. Journal of Neurocytology 26, 423–438.

    Google Scholar 

  • Squire, L. R. (1992) Memory and the hippocampus: A synthesis from findings in rats, monkeys and humans. Psychological Reviews 99, 195–231.

    Google Scholar 

  • Stein, B. A. & Sapolsky, R. M. (1988) Chemical adrenalectomy reduces hippocampal damage induced by kainic acid. Brain Research 473, 175–180.

    Google Scholar 

  • Sterio, D. C. (1984) The unbiased estimation of number and sizes of arbitrary particles using the disector. Journal of Microscopy 134, 127–136.

    Google Scholar 

  • Thoenen, H. (1995) Neurotrophins and neuronal plasticity. Science 270, 593–598.

    Google Scholar 

  • Uylings, H. B. M., Ruiz-marcos, A. & Van Pelt, J. (1986) Themetric analysis of three-dimensional dendritic tree patterns: A methodological review. Journal of Neuroscience Methods 18, 127–151.

    Google Scholar 

  • Vaher, P. R., Luine, V. N., Gould, E. & Mcewen, B. S. (1994) Effects of adrenalectomy on spatial memory performance and dentate gyrus morphology. Brain Research 656, 71–78.

    Google Scholar 

  • Woolley, C. S., Gould, E., Sakai, R. R., Spencer, R. L. & Mc ewen, B. S. (1991) Effects of aldosterone or RU28362 treatment on adrenalectomy-induced cell death in the dentate gyrus of the adult rat. Brain Research 554, 312–315.

    Google Scholar 

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Sousa, N., Madeira, M. & Paula-Barbosa, M. Corticosterone replacement restores normal morphological features to the hippocampal dendrites, axons and synapses of adrenalectomized rats. J Neurocytol 28, 541–558 (1999). https://doi.org/10.1023/A:1007015321767

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