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Journal of Neurocytology

, Volume 29, Issue 5–6, pp 307–326 | Cite as

Steroid synthesis and metabolism in the nervous system: Trophic and protective effects

  • Michael Schumacher
  • Yvette Akwa
  • Rachida Guennoun
  • Françoise Robert
  • Florencia Labombarda
  • Franck Désarnaud
  • Paul Robel
  • Alejandro F. De Nicola
  • Etienne-Emile Baulieu
Article

Abstract

Steroids influence the activity and plasticity of neurons and glial cells during early development, and they continue to exert trophic and protective effects in the adult nervous system. Steroids are produced by the gonads and adrenal glands and reach the brain, the spinal cord and the peripheral nerves via the bloodstream. However, some of them, named “neurosteroids”, can also be synthesized within the nervous system. They include pregnenolone, progesterone, dehydroepiandrosterone and their reduced metabolites and sulfate esters. Little is known concerning the regulation of steroid synthesis in the nervous system, which involves interactions between different cell types. For example, the synthesis of progesterone by Schwann cells in peripheral nerves is regulated by a diffusible neuronal signal. Neurotrophic and neuroprotective effects of steroids have been documented both in cell culture and in vivo. PROG plays an important role in the neurological recovery from traumatic injury of the brain and spinal cord by mechanisms involving protection from excitotoxic cell death, lipid peroxydation and the induction of specific enzymes. After transection of the rat spinal cord, PROG increases the number of nitric oxide synthase expressing astrocytes immediately above and below the lesion. PROG also plays an important role in the formation of new myelin sheaths. This has been shown in the regenerating mouse sciatic nerve after lesion and in cocultures of sensory neurons and Schwann cells. PROG promotes myelination by activating the expression of genes coding for myelin proteins. The modulation of neurostransmitter receptors, in particular the type A γ-aminobutyric acid, the N-methyl-D-aspartate and the sigma 1 receptors, is involved in the psychopharmacological effects of steroids and allows to explain their anticonvulsant, anxiolytic, antidepressive and sedative effects as well as their influence on memory. Pregnenolone sulfate has been shown to reverse age-related deficits in spatial memory performance and to have protective effects on memory in different models of amnesia.

Keywords

Nitric Oxide Spinal Cord Sciatic Nerve Schwann Cell Myelin Sheath 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. ABBASZADE, I. G., CLARKE, T. R., PARK, C. H. J. & PAYNE, A. (1995) The mouse 3?-hydroxysteroid dehydrogenase multigene family includes two functionally distinct groups of proteins. Molecular Endocrinology 9, 1214–1222.PubMedGoogle Scholar
  2. AKWA, Y., SANANES, N., GOUEZOU, M., ROBEL, P., BAULIEU, E. E. & LE GOASCOGNE, C. (1993) Astrocytes and neurosteroids: Metabolism of pregnenolone and dehydroepiandrosterone. Regulation by cell density. Journal of Cell Biology 121, 135–143.PubMedGoogle Scholar
  3. AKWA, Y., PURDY, R., KOOB, G. F. & BRITTON, K. T. (1999) The amygdala mediates the anxiolytic-like effect of the neurosteroid allopregnanolone in rat. Behavioural Brain Research 106, 119–125.PubMedGoogle Scholar
  4. APOSTOLAKIS, E. M., GARAI, J., FOX, C., SMITH, C. L., WATSON, S. J., CLARK, J. H. & O'MALLEY, B. W. (1996) Dopaminergic regulation of progesterone receptors: Brain D5 dopamine receptors mediate induction of lordosis by D1-like agonists in rats. Journal of Neuroscience 16, 4823–4834.PubMedGoogle Scholar
  5. ASBURY, E. T., FRITTS, M. E., HORTON, J. E. & ISAAC, W. L. (1998) Progesterone facilitates the acquisition of avoidance learning and protects against subcortical neuronal death following prefrontal cortex ablation in the rat. Behavioural Brain Research 97, 99–106.PubMedGoogle Scholar
  6. BALTHAZART, J. & BALL, G. F. (1998) New insights into the regulation and function of brain estrogen synthase (aromatase). Trends in Neurosciences 21, 243–249.PubMedGoogle Scholar
  7. BASTIANETTO, S., MONNET, F., JUNIEN, J. L. & QUIRION, R. (1999) Steroidal modulation of sigma receptor function. In Neurosteroids. A New Regulatory Function in the Nervous System (edited by BAULIEU, E. E., ROBEL, P. & SCHUMACHER, M.) pp. 191–205. Totowa, New Jersey: Humana Press.Google Scholar
  8. BAULIEU, E. E., ROBEL, P. & SCHUMACHER, M. (1999) Neurosteroids. A New Regulatory Function in the Nervous System. Totowa, New Jersey: Humana Press.Google Scholar
  9. BAULIEU, E. E. (1991) Neurosteroids: A new function in the brain. Biology of the Cell 71, 3–10.PubMedGoogle Scholar
  10. BAULIEU, E. E. & ROBEL, P. (1995) Non-genomic mechanisms of action of steroid hormones. In Non-Reproductive Actions of Sex Steroids, (edited by BOCK, G. R. & GOODE, J. A.) pp. 24–42. Chichester: John Wiley. Ciba Foundation Symposium 191.Google Scholar
  11. BÄCKSTRÖM, T., ZETTERLUND, B., BLOM, S. & ROMANO, M. (1984) Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with partial epilepsy. Acta Neurologica Scandinavica 69, 240–248.PubMedGoogle Scholar
  12. BEAUJEAN, D., MENSAH-NYAGAN, A. G., DO-REGO, J. L., VAN LUU-THE, PELLETIER, G. & VAUDRY, H. (1999) Immunocytochemical localization and biological activity of hydroxysteroid sulfotransferase in the frog brain. Journal of Neurochemistry 72, 848–857.PubMedGoogle Scholar
  13. BEHL, C., TRAPP, T., SKUTELLA, T. & HOLSBOER, F. (1997) Protection against oxidative stress-induced neuronal cell death?a novel role for RU486. European Journal of Neuroscience 9, 912–920.PubMedGoogle Scholar
  14. BENDER, A. S. & NORENBERG, M. D. (1998) Effect of benzodiazepines and neurosteroids on ammonia-induced swelling in cultured astrocytes. Journal of Neuroscience Research 54, 673–680.PubMedGoogle Scholar
  15. BITRAN, D., HILVERS R. J. & KELLOGG, C. K. (1991) Anxiolytic effects of 3 alpha-hydroxy-5 alpha[beta]-pregnan-20-one: Endogenous metabolites of progesterone that are active at the GABAA receptor. Brain Research 561, 157–161.PubMedGoogle Scholar
  16. BLISS, T. V. P. & COLLINGRIDGE, G. L. (1993) A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 361, 31–39.CrossRefPubMedGoogle Scholar
  17. BOLOGA, L., SHARMA, J. & ROBERTS, E. (1987) Dehydroepiandrosterone and its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures. Journal of Neuroscience Research 17, 225–234.PubMedGoogle Scholar
  18. BOWEN, C. A., PURDY, R. H. & GRANT, K. A. (1999) Ethanol-like discriminative stimulus effects of endogenous neuroactive steroids: Effect of ethanol training dose and dosing procedure. Journal of Pharmacology and Experimental Therapeutics 289, 405–411.PubMedGoogle Scholar
  19. BRANN, D. W., HENDRY, L. B. & MAHESH, V. B. (1995) Emerging diversities in the mechanism of action of steroid hormones. Journal of Steroid Biochemistry and Molecular Biology 52, 113–133.PubMedGoogle Scholar
  20. BROT, M. D., AKWA, Y., PURDY, R. H., KOOB, G. F. & BRITTON, K. T. (1997) The anxiolytic-like effects of the neurosteroid allopregnanolone: Interactions with GABAA receptors. European Journal of Pharmacology 325, 1–7.PubMedGoogle Scholar
  21. CARDOUNEL, A., REGELSON, W. & KALIMI, M. (1999) Dehydroepiandrosterone protects hippocampal neurons against neurotoxin-induced cell death: Mechanism of action. Society of Experimental Biology and Medecine 222, 145–149.Google Scholar
  22. CASCIO, C., PRASAD, V. V. K., LIN, Y. Y., LIEBERMAN, S. & PAPADOPOULOS, V. (1998) Detection of P450c17-independent pathways for dehydroepiandrosterone (DHEA) biosynthesis in brain glial tumor cells. Proceedings of the National Academy of Sciences of the USA 95, 2862–2867.PubMedGoogle Scholar
  23. CELOTTI, F., MELCANGI, R. C. & MARTINI, L. (1992) The 5?-reductase in the brain: Molecular aspects and relation to brain function. Frontier of Neuroendocrinology 13, 163–215.Google Scholar
  24. CHAN, J. R., PHILLIPS, L. J. & GLASER, M. (1998) Glucocorticoids and progestins signal the initiation and enhance the rate of myelin formation. Proceedings of the National Academy of Sciences of the USA 95, 10459–10464.PubMedGoogle Scholar
  25. CHAO, C. C., HU, S., SHENG, W. S., BU, D., BUKRINSKY, M. I. & PETERON, P. K. (1996) Cytokine-stimulated astrocytes damage human neurons via nitric oxide mechanism. Glia 16, 276–284.PubMedGoogle Scholar
  26. CHOI, D. W. (1993) Nitric oxide: Foe or friend to the injured brain? Proceedings of the National Academy of Sciences of the USA 90, 9741–9743.PubMedGoogle Scholar
  27. COMPAGNONE, N. A. & MELLON, S. H. (1998) Dehydroepiandrosterone: A potential signalling molecule for neocortical organization during development. Proceedings of the National Academy of Sciences of the USA 95, 4678–4683.PubMedGoogle Scholar
  28. COMPAGNONE, N. A., SALIDO, E., SHAPIRO, L. J. & MELLON, S. H. (1997) Expression of steroid sulfatase during embryogenesis. Endocrinology 138, 4768–4773.PubMedGoogle Scholar
  29. COMPAGNONE, N. A., BULFONE, A., RUBENSTEIN, J. L. R. & MELLON, S. H. (1995) Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system. Endocrinology 136, 5212–5222.PubMedGoogle Scholar
  30. CORPÉCHOT, C., ROBEL, P., AXELSON, M., SJÖVALL, J., BAULIEU, E. E. (1981) Characterization and measurement of dehydroepiandrosterone sulfate in the rat Trophic effects of steroids 321 brain. Proceedings of the National Academy of Sciences of the USA 78, 4704–4707.PubMedGoogle Scholar
  31. CULTY, M., LI, H., BOUJRAD, N., AMRI, H., VIDIC, B., BERNASSAU, J. M., REVERSAT, J. L. & PAPADOPOULOS, V. (1999) In vitro studies on the role of the peripheral-type benzodiazepine receptor in steroidogenesis. Journal of Steroid Biochemistry and Molecular Biology 69, 123–130.PubMedGoogle Scholar
  32. DAR, M. S. (1995) Antagonism by intracerebellar Ro15–4513 of acute ethanol-induced motor incoordination in mice. Pharmacology, Biochemistry and Behavior 52, 217–223.Google Scholar
  33. DARNAUDÉRY, M., KOEHL, M., PALLARÉS, M., LE MOAL, M. & MAYO, W. (1998) The neurosteroid pregnenolone sulfate increases cortical acetylcholine release: A microdialysis study in freely moving rats. Journal of Neurochemistry 71, 2018–2022.PubMedGoogle Scholar
  34. DE KLOET, E. R., VREUGDENHIL, E., OITZL, M. S. & JOËLS, M. (1998) Brain corticosteroid receptor balance in health and disease. Endocrine Reviews 19, 269–301.PubMedGoogle Scholar
  35. DE NICOLA, A. F. (1993) Steroid Hormones and Neuronal Regeneration. Advances in Neurology 59, 199–206.PubMedGoogle Scholar
  36. DE NICOLA, A. F., FERRINI, M., GONZALEZ, S. L., GONZALEZ, D., GRILLO, C. A., PIROLI, G., SARAVIA, F. & DE KLOET, E. R. (1998) Regulation of gene expression by corticoid hormones in the brain and spinal cord. Journal of Steroid Biochemistry and Molecular Biology 65, 253–272.PubMedGoogle Scholar
  37. DEL CERRO, S., GARCIA-ESTRADA, J. & GARCIASEGURA, L. M. (1995) Neuroactive steroids regulate astroglia morphology in hippocampal cultures from adult rats. Glia 14, 65–71.PubMedGoogle Scholar
  38. DEVAUD, L. L., PURDY, R. H., FINN, D. A. & MORROW, A. L. (1996) Sensitization of ?-aminobutyric acidA receptors to neuroactive steroids in rats during ethanol withdrawal. Journal of Pharmacology and Experimental Therapeutics 278, 510–517.PubMedGoogle Scholar
  39. DÉSARNAUD, F., DO THI, A. N., BROWN, A., LEMKE, G., SUTER, U., BAULIEU, E. E. & SCHUMACHER, M. (1998) Progesterone stimulates the activity of the promoters of peripheral myelin protein-22 and P0 genes in Schwann cells. Journal of Neurochemistry 71, 1765–1768.PubMedGoogle Scholar
  40. ENDOH, M., MAIESE, K. & WAGNER, J. (1994) Expression of the inducible form of nitric oxide synthase by reactive astrocytes after transient global ischemia. Brain Research 651, 92–100.PubMedGoogle Scholar
  41. EVANS, R. M. (1988) The steroid thyroid hormone receptor superfamily. Science 240, 889–895.Google Scholar
  42. FAWCETT, J. W. & KEYNES, R. J. (1990) Peripheral nerve regeneration. Annual Review of Neurosciences 13, 43–60.Google Scholar
  43. FAZEKAS, F., SCHMIDT, R., KLEINERT, R., KAPELLER, P., ROOB, G. & FLOOH, E. (1998) The spectrumof ageassociated brain abnormalities: Their measurement and histopathological correlates. Journal of Neural Transmission Supplement 53, 31–39.PubMedGoogle Scholar
  44. FLOOD, J. F., MORLEY, J. E. & ROBERTS, E. (1992) Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proceedings of the National Academy of Sciences of the USA 89, 1567–1571.PubMedGoogle Scholar
  45. FLOOD, J. F., MORLEY, J. E. & ROBERTS, E. (1995) Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures: The amygdala is by far the most sensitive. Proceedings of the National Academy of Sciences of the USA 92, 10806–10810.PubMedGoogle Scholar
  46. FRYE, C. A. & BAYON, L. E. (1998) Seizure activity is increased in endocrine states characterized by decline in endogenous levels of the neurosteroid 3 alpha, 5 alpha-THP. Neuroendocrinology 68, 272–280.PubMedGoogle Scholar
  47. FRYE, C. A. & BAYON, L. E. (1999) Cyclic withdrawal from endogenous and exogenous progesterone increases kainic acid and perforant pathway induced seizures. Pharmacology, Biochemistry and Behavior 62, 315–321.Google Scholar
  48. FULOP, Z. L., WRIGHT, D. W. & STEIN, D. G. (1998) Pharmacology of traumatic brain injury: Experimental models and clinical implications. Neurological Report 22, 100–109.Google Scholar
  49. FURUKAWA, A., MIYATAKE, A., OHNISHI, T. & ICHIKAWA, Y. (1998) Steroidogenic acute regulatory protein (StAR) transcripts constitutively expressed in the adult rat central nervous system: Colocalization of StAR, cytochrome P-450SCC (CYP XIA1), and 3?-hydroxysteroid dehydrogenase in the rat brain. Journal of Neurochemistry 71, 2231–2238.PubMedGoogle Scholar
  50. GALIÈGUE, S., JBILO, O., COMBES, T., BRIBES, E., CARAYON, P., LE FUR, G. & CASELLAS, P. (1999) Cloning and characterization of PRAX-1. A new protein that specifically interacts with the peripheral benzodiazepine receptor. Journal of Biological Chemistry 274, 2938–2952.PubMedGoogle Scholar
  51. GALLAGHER, M., LANDFIELD, W., MCEWEN, B., MEANEY M. J., RAPP, P. R., SAPOLSKY, R. & WEST, M. J. (1996) Hippocampal neurodegeneration in aging. Science 274, 484–485.Google Scholar
  52. GARCIA-ESTRADA, J., LUQUIN, S., FERNANDEZ, A. M. & GARCIA-SEGURA, L. M. (1999) Dehydroepiandrosterone, pregnenolone and sex steroids down-regulate reactive astroglia in the male rat brain after a penetrating brain injury. International Journal of Developmental Neurosciences 17, 145–151.Google Scholar
  53. GARCIA-SEGURA, L. M., CARDONA-GOMEZ, P., NAFTOLIN, F. & CHOWEN, J. A. (1998) Estradiol upregulates Bcl-2 expression in adult brain neurons. NeuroReport 9, 593–597.PubMedGoogle Scholar
  54. GARCIA-SEGURA, L. M., NAFTOLIN, F., HUTCHISON, J. B., AZCOITIA, I. & CHOWEN, J. A. (1999) Role of astroglia in estrogen regulation of synaptic plasticity and brain repair. Journal of Neurobiology 40, 574–584.PubMedGoogle Scholar
  55. GEHLERT, D. R., STEPHENSON, D. T., SCHOBER, D. A., RASH, K. & CLEMENS, J. A. (1997) Increased expression of peripheral benzodiazepine receptors in the facial nucleus following motor neuron axotomy. Neurochemistry International 31, 705–713.PubMedGoogle Scholar
  56. GOUJET-ZALC, C., BABINET, C., MONGE, M., TIMSIT, S., CABON, F., GANSMULLER, A., MIURA, M., SANCHEZ, M., POURNIN, S., MIKOSHIBA, K. & ZALC, B. (1993) The proximal region of the MBP gene promoter is sufficient to induce oligodendroglial-specific expression in transgenic mice. European Journal of Neurosciences 5, 624–632.Google Scholar
  57. GRANT, K. A., AZAROV, A., BOWEN, C. A., MIRKIS, S. & PURDY, R. H. (1996) Ethanol-like discriminative stimulus effects of the neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one in female Macaca fascicularis monkeys. Psychopharmacology 124, 340–346.PubMedGoogle Scholar
  58. GRONEMEYER, H. (1992) Control of transcription activation by steroid hormone receptors. FASEB Journal 6, 2524–2529.PubMedGoogle Scholar
  59. GUARNERI, P., GUARNERI, R., CASCIO, C., PICCOLI, F. & PAPADOPOULOS, V. (1995) ?-aminobutyric acid type A/benzodiazepine receptors regulate rat retina neurosteroidogenesis. Brain Research 683, 65–72.PubMedGoogle Scholar
  60. GUENNOUN, R., FIDDES, R. J., GOUÉZOU, M., LOMBÈS, M. & BAULIEU, E. E. (1995) A key enzyme in the biosynthesis of neurosteroids, 3?-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3?-HSD), is expressed in rat brain. Molecular Brain Research 30, 287–300.PubMedGoogle Scholar
  61. GUENNOUN, R., SCHUMACHER, M., ROBERT, F., DELESPIERRE, B., GOUÉZOU, M., EYCHENNE, B., AKWA, Y., ROBEL, P. & BAULIEU, E. E. (1997) Neurosteroids: Expression of functional 3?-hydroxysteroid dehydrogenase by rat sensory neurons and Schwann cells. European Journal of Neuroscience 9, 2236–2247.PubMedGoogle Scholar
  62. GUTH, L., ZHANG, Z. & ROBERTS, E. (1994) Key role for pregnenolone in combination therapy promotes recovery after spinal cord injury. Proceedings of the National Academy of Sciences of the USA 91, 12308–12312.PubMedGoogle Scholar
  63. HAWKIN, R. D., KANDEL, E. R., SIEGELBAUM, S. A. (1993) Learning to modulate transmitter release: Themes and variations on synaptic plasticity. Annual Review of Neurosciences 16, 625–665.Google Scholar
  64. HERZOG, A. G. (1999) Psychoneuroendocrine aspects of temporolimbic epilepsy. Part I. Brain, reproductive steroids, and emotions. Psychosomatics 40, 95–101.PubMedGoogle Scholar
  65. ISAACSON, R. L., YODER, P. E. & VARNER, J. (1994) The effects of pregnenolone on acquisition and retention of a food search task. Behavioral and Neural Biology 61, 170–176.PubMedGoogle Scholar
  66. ITO, K., SKINKLE, K. L. & HICKS, T. P. (1999) Age dependent, steroid-specific effects of oestrogen on longterm potentiation in rat hippocampal slices. Journal of Physiology (London) 515, 209–220.Google Scholar
  67. JIANG, N., CHOPP, M., STEIN, D. G. & FELDBLUM, S. (1996) Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats. Brain Research 735, 101–107.PubMedGoogle Scholar
  68. JOHNSTON, G. A. (1996) GABAc receptors: Relatively simple transmitter-gated ion channels? Trends in Pharmacological and Experimental Therapeutics 17, 319–323.Google Scholar
  69. JUNG-TESTAS, I., SCHUMACHER, M., ROBEL, P. & BAULIEU, E. E. (1996a) Demonstration of progesterone receptors in rat Schwann cells. Journal of Steroid Biochemistry and Molecular Biology 58, 77–82.PubMedGoogle Scholar
  70. JUNG-TESTAS, I., SCHUMACHER, M., ROBEL, P. & BAULIEU, E. E. (1996b) The neurosteroid progesterone increases the expression of myelin proteins (MBP and CNPase) in rat oligodendrocytes in primary culture. Cellular and Molecular Neurobiology 16, 439–443.PubMedGoogle Scholar
  71. JUNG-TESTAS, I., HU, Z. Y., ROBEL, P. & BAULIEU, E. E. (1989) Biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells. Endocrinology 125, 2083–2091.PubMedGoogle Scholar
  72. JUNG-TESTAS, I., RENOIR, J. M., GASC, J. M. & BAULIEU, E. E. (1991) Estrogen-inducible progesterone receptor in primary cultures of rat glial cells. Experimental Cell Research 193, 12–19.PubMedGoogle Scholar
  73. KATO, J., HIRATA, S., NOZAWA, A. & YAMADAMOURI, N. (1994) Gene expression of progesterone receptor isoforms in the rat brain. Hormones and Behavior 28, 454–463.PubMedGoogle Scholar
  74. KOENIG, H., SCHUMACHER, M., FERZAZ, B., DO THI, A. N., RESSOUCHES, A., GUENNOUN, R., JUNGTESTAS, I., ROBEL, P., AKWA, Y. & BAULIEU, E. E. (1995) Progesterone synthesis and myelin formation by Schwann cells. Science 268, 1500–1503.PubMedGoogle Scholar
  75. KOHCHI, C., UKENA, K. & TSUTSUI, K. (1998) Age-and region-specific expressions of the messenger RNAs encoding for steroidogenic enzymes P450scc, P450c17 and 3?-HSD in the postnatal rat brain. Brain Research 801, 233–238.PubMedGoogle Scholar
  76. KOKATE, T. G., BANKS, M. K., MAGEE, T., YAMAGUCHI, S., ROGAWSKI, M. A. (1999) Finasteride, a 5?-reductase inhibitor, blocks the anticonvulsant activity of progesterone in mice. Journal of Pharmacology and Experimental Therapeutics 288, 679–684.PubMedGoogle Scholar
  77. KORNEYEV, A., PAN, B. S., POLO, A., ROMEO, E., GUIDOTTI, A. & COSTA, E. (1993) Stimulation of brain pregnenolone synthesis by mitochondrial diazepam binding inhibitor receptor ligands in vivo. Journal of Neurochemistry 61, 1515–1524.PubMedGoogle Scholar
  78. KRIEGER, N. R. & SCOTT, R. G. (1989) Nonneuronal localization for steroid converting enzyme: 3?-Hydroxysteroid oxidoreductase in olfactory tubercle of rat brain. Journal of Neurochemistry 52, 1866–1870.PubMedGoogle Scholar
  79. KUHLMANN, A. C. & GUILARTE, T. R. (1997) The peripheral benzodiazepine receptor is a sensitive indicator of domoic acid neurotoxicity. Brain Research 751, 281–288.PubMedGoogle Scholar
  80. KUHLMANN, A. C. & GUILARTE, T. R. (1999) Regional and temporal expression of the peripheral benzodiazepine receptor in MPTP neurotoxicity. Toxicology and Science 48, 107–116.Google Scholar
  81. LABOMBARDA, F., GUENNOUN, R., GONZALEZ, S., ROIG, P., LIMA, A., SCHUMACHER, M. & DE NICOLA, A. F. (2000a) Immunocytochemical evidence for a progesterone receptor in neurons and glial cells of the rat spinal cord. Neuroscience Letters, in press.Google Scholar
  82. LABOMBARDA, F., GONZALEZ, S., ROIG, P., LIMA, A, GUENNOUN, R., SCHUMACHER, M. & DE NICOLA, A. F. (2000b) Progesterone-induced changes of NADPH-diaphorase and glial fibrillary acidic protein in astrocytes from normal and injured rat spinal cord. Journal of Neurochemistry, in press.Google Scholar
  83. LACOR, P., BENAVIDES, J. & FERZAZ, B. (1996) Enhanced expression of the peripheral benzodiazepine receptor (PBR) and its endogenous ligand octadecaneuropeptide (ODN) in the regenerating adult rat sciatic nerve. Neuroscience Letters 220, 61–65.PubMedGoogle Scholar
  84. LACOR, P., GANDOLFO, P., TONON, M. C., BRAULT, E., DALIBERT, I., SCHUMACHER, M., BENAVIDES, J. & FERZAZ, B. (1999) Regulation of the expression of peripheral benzodiazepine receptors and their endogenous ligands during rat sciatic nerve degeneration and regeneration: A role for PBR in neurosteroidogenesis. Brain Research 815, 70–80.PubMedGoogle Scholar
  85. LADURELLE, N., EYCHENNE, B., DENTON, D., BLAIRWEST, J., SCHUMACHER, M., ROBEL, P. & BAULIEU, E. E. (2000) Prolonged intracerebroventricular infusion of neurosteroids affects cognitive Trophic effects of steroids 323 performances in the mouse. Brain Research 858, 371–379.PubMedGoogle Scholar
  86. LAMBERT, J. J., BELLELI, D., SHEPHERD, S. E, PISTIS, M. & PETERS, J. A. (1999) The selective interaction of neurosteroids with theGABAA receptor. In Neurosteroids. A New Regulatory Function in the Nervous System (edited by BAULIEU, E. E., ROBEL, P. & SCHUMACHER, M.) pp. 125–142. Totowa, New Jersey: Humana Press.Google Scholar
  87. LE GOASCOGNE, C., EYCHENNE, B., TONON, M. C., LACHAPELLE, F., BAUMANN, N. & ROBEL, P. (2000) Neurosteroid progesterone is up-regulated in the brain of Jimpy and Shiverer mice. Glia 29, 14–24.PubMedGoogle Scholar
  88. LE GOASCOGNE, C., ROBEL, P., GOUÉZOU, M., SANANÈS, N., BAULIEU, E. E. & WATERMAN, M. (1987) Neurosteroids: Cytochrome P450scc in rat brain. Science 237, 1212–1215.PubMedGoogle Scholar
  89. LE GOASCOGNE, C., GOUÉZOU, M., ROBEL, P., DEFAYE, G., CHAMBAZ, E., WATERMAN, M. R. & BAULIEU, E. E. (1989) The cholesterol side-chain cleavage complex in human brain white matter. Journal of Neuroendocrinology 1, 153–156.Google Scholar
  90. LEMKE, G. (1993) The molecular genetics of myelination: An update. Glia 7, 263–271.PubMedGoogle Scholar
  91. LI, P. K., RHODES, M. E., JAGANNATHAN, S. & JOHNSON, D. A. (1995) Reversal of scopolamine induced amnesia in rats by the steroid sulfatase inhibitor estrone-3-O-sulfamate. Brain Research and Cognitive Brain Research 2, 251–254.Google Scholar
  92. MACLUSKY, N. J. & MCEWEN, B. S. (1980) Progestin receptors in rat brain: Distribution and properties of cytoplasmic progestin-binding sites. Endocrinology 106, 192–202.PubMedGoogle Scholar
  93. MAJEWSKA, M. D. (1992) Neurosteroids: Endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Progress in Neurobiology 38, 379–395.PubMedGoogle Scholar
  94. MAJEWSKA, M. D., HARRISON, N. L. S., BARKER, J. L. & PAUL, S. M. (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232, 1004–1007.Google Scholar
  95. MATHIS, C., PAUL, S. M. & CRAWLEY, J. N. (1994) The neurosteroid pregnenolone sulfate blocks NMDA antagonist?induced deficits in a passive avoidance memory task. Psychopharmacology 116, 201–206.PubMedGoogle Scholar
  96. MAURICE, T., SU, T. P. & PRIVAT, A. (1998) ?1 (sigma 1) receptor agonists and neurosteroids attenuate B25–35-amyloid peptide-induced amnesia in mice through a common mechanism. Neuroscience 83, 413–428.PubMedGoogle Scholar
  97. MAYO, W., DELLU, F., ROBEL, P., CHERKAOUI, J., LE MOAL, M., BAULIEU, E. E. & SIMON, H. (1993) Infusion of neurosteroids into the nucleus basalis magnocellularis affects cognitive processes in the rat. Brain Research 607, 324–328.PubMedGoogle Scholar
  98. MAYO, W., VALLEE, M., DARNAUDÉRY, M., LE MOAL, M. (1999) Neurosteroids: Behavioral studies. In Neurosteroids. A New Regulatory Function in the Nervous System. (edited by BAULIEU, E. E., ROBEL, P. & SCHUMACHER, M.) pp. 317–336. Totowa, New Jersey: Humana Press.Google Scholar
  99. MCEWEN, B. S. (1997) The brain is an important target of adrenal steroid actions. A comparison of synthetic and natural steroids. Annals of the New York Academic of Sciences 823, 201–213.Google Scholar
  100. MCEWEN, B. S. (1999) Gonadal hormone regulation of synaptic plasticity in the brain: What is the mechanism? In Neurosteroids. A New Regulatory Function in the Nervous System. (edited by BAULIEU, E. E., ROBEL, P. & SCHUMACHER, M.) pp. 233–254. Totowa, New Jersey: Humana Press.Google Scholar
  101. MCEWEN, B. S. & ALVES, S. E. (1999) Estrogen actions in the central nervous system. Endocrine Reviews 20, 279–307.PubMedGoogle Scholar
  102. MCKINNEY, M., COYLE, J. T. & HEDREEN, J. C. (1983) Topographic analysis of the innervation of the rat neocortex and hippocampus by the basal forebrain cholinergic system. Journal of Comparative Neurology 217, 103–121.PubMedGoogle Scholar
  103. MELCANGI, R. C., POLETTI, A., CAVARRETTA, I., CELOTTI, F., COLCIAGO, A., MAGNAGHI, V., MOTTA, M., NEGRI-CESI, P. & MARTINI, L. (1998a) The 5alpha-reductase in the central nervous system: Expression and modes of control. Journal of Steroid Biochemistry and Molecular Biology 65, 295–299.PubMedGoogle Scholar
  104. MELCANGI, R. C., MAGNAGHI, V., CAVARRETTA, I., MARTINI, L. & PIVA, F. (1998b) Age-induced decrease of glycoprotein P0 and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives. Neuroscience 85, 569–578.PubMedGoogle Scholar
  105. MELCANGI, R. C, MAGNAGHI, V., CAVARRETTA, I., ZUCCHI, I., BOVOLIN, P., DÕURSO, D. & MARTINI, L. (1999) Progesterone derivatives are able to influence peripheral myelin protein 22 and P0 gene expression: Possible mechanisms of action. Journal of Neuroscience Research 56, 349–357.PubMedGoogle Scholar
  106. MESSING, A., BEHRINGER, R. R., HAMMANG, J. P., PALMITER, R. D., BRINSTER, R. L. & LEMKE, G. (1992) P0 promoter directs expression of reporter and toxin genes to Schwann cells of transgenic mice. Neuron 8, 507–520.PubMedGoogle Scholar
  107. MEZIANE, H., MATHIS, C., PAUL, S. M. & UNGERER, A. (1996) The neurosteroid pregnenolone sulfate reduces learning deficits induced by scopolamine and has promnestic effects in mice performing an appetitive learning task. Psychopharmacology 126, 323–330.PubMedGoogle Scholar
  108. MILLER, W. L. & STRAUSS, J. F. (1999) Molecular pathology and mechanism of action of the steroidogenic acute regulatory protein, StAR. Journal of Steroid Biochemistry and Molecular Biology 69, 131–141.PubMedGoogle Scholar
  109. MORAN, M. H. & SMITH, S. S. (1998) Progesterone withdrawal I: Pro-Convulsant effects. Brain Research 807, 84–90.PubMedGoogle Scholar
  110. MORRELL, M. J. (1999) Epilepsy in women: The science of why it is special. Neurology 53, S42-S48.PubMedGoogle Scholar
  111. MORRIS, K. D. W., MOOREFIELD, C. & AMIN, J. (1999) Differential modulation of the ?-aminobutyric acid type C receptor by neuroactive steroids. Molecular Pharmacology 56, 752–759.PubMedGoogle Scholar
  112. MORRIS, R. G. M., ANDERSON, E., LYNCH, G. S. & BAUDRY, M. (1986) Selective impairment of learning and blockade of long-term potentiation by an Nmethyl-D-aspartate receptor antagonist, AP5. Nature 319, 774–776.Google Scholar
  113. MURAKAMI, K., FELLOUS, A., BAULIEU, E. E. & ROBEL, P. (2000) Pregnenolone binds to microtubuleassociated protein 2 and stimulates microtubule assembly. Proceedings of the National Academy of Sciences of the USA 97, 3579–3584.PubMedGoogle Scholar
  114. NIEHOFF, D. L. & KUHAR, M. J. (1983) Benzodiazepine receptors: Localization in the rat amygdala. Journal of Neuroscience 3, 2091–2097.PubMedGoogle Scholar
  115. NOTTERPEK, L., SNIPES, G. J. & SHOOTER, E. M. (1999) Temporal expression pattern of peripheral myelin protein 22 during in vivo and in vitro myelination. Glia 25, 358–369.PubMedGoogle Scholar
  116. OGATA, T., NAKAMURA, Y., TSUJI K. et al. (1993) Steroid hormones protect spinal cord neurons from glutamate toxicity. Neuroscience 55, 445–449.PubMedGoogle Scholar
  117. PALLARÉ S, M., DARNAUDÉRY, M., DAY, J., LE MOAL, M. & MAYO, W. (1998) The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory. Neuroscience 87, 551–558.PubMedGoogle Scholar
  118. PAPADOPOULOS, V., AMRI, H., LI, H., BOUJRAD, N., VIDIC, B. & GARNIER, M. (1997) Targeted disruption of the peripheral-type benzodiazepine receptor gene inhibits steroidogenesis in the R2C Leydig tumor cell line. Journal of Biological Chemistry 272, 32129–32135.PubMedGoogle Scholar
  119. PAPADOPOULOS, V. (1993) Peripheral-type benzodiazepine/ diazepam binding inhibitor receptor-biological role in steroidogenic cell function. Endocrine Reviews 14, 222–240.PubMedGoogle Scholar
  120. PAPADOPOULOS, V. & GUARNERI, P. (1994) Regulation of C6 glioma cell steroidogenesis by adenosine 3?,5?-cyclic monophosphate. Glia 10, 75–78.PubMedGoogle Scholar
  121. PARK-CHUNG, M., MALAYEV, A., PURDY, R. H., GIBBS, T. T. & FARB, D. H. (1999) Sulfated and unsulfated steroids modulate gamma-aminobutyric acidA receptor function through distinct sites. Brain Research 830, 72–87.PubMedGoogle Scholar
  122. PAUL, S. M. & PURDY, R. H. (1992) Neuroactive steroids. FASEB Journal 6, 2311–2322.PubMedGoogle Scholar
  123. PAVLIDES, C., OGAWA., S., KIMURA, A. & MCEWEN, B. S. (1996) Role of adrenal steroid mineralocorticoid and glucocorticoid receptors in long-term potentiation in the CA1 field of hippocampal slices. Brain Research 738, 229–235.PubMedGoogle Scholar
  124. PETERS, A. (1996) Age-related changes in oligodendrocytes in monkey cerebral cortex. Journal of Comparative Neurology 371, 153–163.PubMedGoogle Scholar
  125. PHAN, V. L., SU, T. P., PRIVAT, A. & MAURICE, T. (1999) Modulation of steroidal levels by adrenalectomy/ castration and inhibition of neurosteroid synthesis enzymes affect sigma1 receptor-mediated behaviour in mice. European Journal of Neuroscience 11, 2385–2396.PubMedGoogle Scholar
  126. POWER, R. F., CONNEELY, O. M. & O'MALLEY, B. W. (1992) New insights into activation of the steroid hormone receptor superfamily. Trends in Pharmacological Sciences 13, 318–323.PubMedGoogle Scholar
  127. PURDY, R. H. & PAUL, S. M. (1999) Potentiation of GABAergic neurotransmission by steroids. In Neurosteroids. A New Regulatory Function in the Nervous System (edited by BAULIEU, E. E., ROBEL, P. & SCHUMACHER, M.) pp. 143–153. Totowa, New Jersey: Humana Press.Google Scholar
  128. RAJKOWSKI, K., ROBEL, P. & BAULIEU, E. E. (1997) Hydroxysteroid sulfotransferase activity in the rat brain and liver as a function of age and sex. Steroids 62, 427–436.PubMedGoogle Scholar
  129. RAPP, P. R. & GALLAGHER, M. (1996) Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proceedings of the National Academy of Sciences of the USA 93, 9926–9930.PubMedGoogle Scholar
  130. REDDY, D. S. & KULKARNI, S. K. (1998) Proconvulsant effects of neurosteroids pregnenolone sulfate and dehydroepiandrosterone sulfate in mice. European Journal of Pharmacology 345, 55–59.PubMedGoogle Scholar
  131. RHODES, M. E., LI, P. K., BURKE, A. M. & JOHNSON, D. A. (1997) Enhanced plasma DHEAS, brain acetylcholine and memory mediated by steroid sulfatase inhibition. Brain Research 773, 28–32.PubMedGoogle Scholar
  132. ROBEL, P., SCHUMACHER, M. & BAULIEU, E. E. (1999) Neurosteroids: From definition and biochemistry to physiopathologic function. In Neurosteroids. A New Regulatory Function in the Nervous System. (edited by BAULIEU, E. E, ROBEL, P. & SCHUMACHER, M.) pp. 1–25. Totowa, New Jersey: Humana Press.Google Scholar
  133. ROBERT, F., GUENNOUN, R., DÉ SARNAUD, F., DO THI, A. N., BENMESSAHEL, Y., BAULIEU, E. E. & SCHUMACHER, M. (2000) Synthesis of progesterone in Schwann cells: Regulation by neurons. Eur. J. Neurosci., in press.Google Scholar
  134. RODGERS, R. J. & JOHNSON, N. J. (1998) Behaviorally selective effects of neuroactive steroids on plus-maze anxiety in mice. Pharmacology, Biochemistry and Behavior 59, 221–232.Google Scholar
  135. ROMEO, E., STRÖHLE, A., SPALLETTA, G., DI MICHELE, F., HERMANN, B., HOLSBOER, F., PASINI, A. & RUPPRECHT, R. (1998) Effects of antidepressant treatment on neuroactive steroids in major depression. American Journal of Psychiatry 155, 910–913.PubMedGoogle Scholar
  136. ROOF, R. L., DUVDEVANI, R. & STEIN, D. G. (1993) Gender influences outcome of brain injury-Progesterone plays a protective role. Brain Research 607, 333–336.Google Scholar
  137. ROOF, R. L., DUVDEVANI, R, BRASWELL, L. & STEIN, D. G. (1994) Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats. Experimental Neurology 129, 64–69.PubMedGoogle Scholar
  138. ROOF, R. L., HOFFMAN, S. W. & STEIN, D. G. (1997) Progesterone protects against lipid peroxidation following traumatic brain injury in rats. Molecular and Chemical Neuropathology 31, 1–11.Google Scholar
  139. ROOF, R. L., DUVDEVANI, R., HEYBURN, J. W. & STEIN, D. G. (1996) Progesterone rapidly decreases brain edema: Treatment delayed up to 24 hours is still effective. Experimental Neurology 138, 246–251.PubMedGoogle Scholar
  140. RUPPRECHT, R. & HOLSBOER, F. (1999) Neuroactive steroids: Mechanisms of action and neuropsychopharmacological perspectives. Trends in Neurosciences 22, 410–416.PubMedGoogle Scholar
  141. RUPPRECHT, R., REUL, J. M. H. M., TRAPP, T., VAN STEENSEL, B., WETZEL, C., DAMM, K., ZIEGELGÄNSBERGER, W. & HOLSBOER, F. (1993) Progesterone receptor-mediated effects of neuroactive steroids. Neuron 11, 523–530.PubMedGoogle Scholar
  142. SANDERS, S. K. & SHEKHAR, A. (1995) Regulation of anxiety by GABAA receptors in the amygdala. Pharmacology, Biochemistry and Behavior 52, 701–706.Google Scholar
  143. SCHUMACHER, M. (1990) Rapid membrane effects of steroid hormones: An emerging concept in neuroendocrinology. Trends in Neurosciences 13, 359–362.PubMedGoogle Scholar
  144. SMITH, G. B. & OLSEN, R. W. (1995) Functional domains of GABAA receptors. Trends in Pharmacological Sciences 16, 162–167.PubMedGoogle Scholar
  145. SMITH, S. S. (1991) Progesterone administration attenuates excitatory amino acid responses of cerebellar Purkinje cells. Neuroscience 42, 309–320.PubMedGoogle Scholar
  146. SOHRABJI, F., MIRANDA, R. C. J. & TORANALLERAND, C. D. (1995) Identification of a putative estrogen response element in the gene encoding brainderived neurotrophic factor. Proceedings of the National Academy of Sciences of the USA 92, 11110–11114.PubMedGoogle Scholar
  147. STEIN D. G. & FULOP, Z. L. (1998) Progesterone and recovery after traumatic brain injury. The Neuroscientist 4, 435–442.Google Scholar
  148. STEPHENSON, A. F. (1995) The GABAA receptors. Biochemical Journal 310, 1–9.PubMedGoogle Scholar
  149. STOCCO, D. M. (1997) A Star search: Implications in controlling steroidogenesis. Journal of Steroid Biochemistry and Molecular Biology 69, 131–141.Google Scholar
  150. STOJKOVIC, T., COLIN, C., LE SAUX, F. & JACKE, C. (1998) Specific pattern of nitric oxide synthase expression in glial cells after hippocampal injury. Glia 22, 329–337.PubMedGoogle Scholar
  151. STRÖHLE, A., ROMEO, E., HERMANN, B., PASINI, A., SPALLETTA, G., DI MICHELE, F., HOLSBOER, F. & RUPPRECHT, R. (1999) Concentrations of 3 alphareduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery. Biological Psychiatry 45, 274–277.PubMedGoogle Scholar
  152. STRÖMSTEDT, M. & WATERMAN, M. R. (1995) MessengerRNAsencoding steroidogenic enzymes are expressed in rodent brain. Molecular Brain Research 34, 75–88.PubMedGoogle Scholar
  153. SUTER, U. & SNIPES, G. J. (1995) Biology and genetics of hereditary motor and sensory neuropathies. Annual Review of Neuroscience 18, 45–75.PubMedGoogle Scholar
  154. SUTER, U., SNIPES, G. J., SCHOENER-SCOTT, R., WELCHER, A. A., PAREEK, S., LUPSKI, J. R., MURPHY, R. A., SHOOTER, E. M. & PATEL, P. I. (1994) Regulation of tissue-specific expression of alternative peripheral myelin protein-22 (PMP22) gene transcripts by two promoters. Journal of Biological Chemistry 269, 25795–25808.PubMedGoogle Scholar
  155. SUZDAK, P. D., GLOWA, J. R., CRAWLEY, J. N., SCHWARTZ, R. D., SKOLNICK, P. & PAUL, S. M. (1986) A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 234, 1243–1247.PubMedGoogle Scholar
  156. TAKASE, M., UKENA, K., YAMAZAKI, T., KOMINAMI, S. & TSUTSUI, K. (1999) Pregnenolone, pregnenolone sulfate, and cytochrome P450 side-chain cleavage enzyme in the amphibian brain and their seasonal changes. Endocrinology 140, 1936–1944.PubMedGoogle Scholar
  157. THOMAS, A. J., NOCKELS, R. P., PAN, H. Q., SHAFFREY, C. I. & CHOPP, M. (1999) Progesterone is neuroprotective after acute experimental spinal cord trauma in rats. Spine 24, 2134–2138.PubMedGoogle Scholar
  158. TOPILKO, P., SCHNEIDER-MAUNOURY, S., LEVI, G., BARON-VAN EVERCOOREN, A., CHENNOUFI, A. B. Y., SEITANIDOU, T., BABINET, C. & CHARNAY, P. (1994) Krox-20 controls myelination in the peripheral nervous system. Nature 371, 796–799.PubMedGoogle Scholar
  159. TORAN-ALLERAND, C. D. (1999) Novel mechanisms of estrogen action in the developing brain: The role of steroid/neurotrophin interactions. In Neurosteroids. A New Regulatory Function in the Nervous System. (edited by BAULIEU, E. E., ROBEL, P. & SCHUMACHER, M.) pp. 293–316. Totowa, New Jersey: Humana Press.Google Scholar
  160. TORAN-ALLERAND, C. D., SINGH, M. & SÉTQLÓ, G. J. (1999) Novel mechanisms of estrogen action in the brain: New players in an old story. Frontiers in Neuroendocrinology 20, 97–121.PubMedGoogle Scholar
  161. TRUSS, M. & BEATO, M. (1993) Steroid hormone receptors: Interaction with deoxyribonucleic acid and transcription factors. Endocrine Reviews 14, 459–479.PubMedGoogle Scholar
  162. TSUTSUI, K. & YAMAZAKI, T. (1995) Avian neurosteroids. I. Pregnenolone biosynthesis in the quail brain. Brain Research 678, 1–9.PubMedGoogle Scholar
  163. URANI, A., PRIVAT, A. & MAURICE, T. (1998) The modulation by neurosteroids of the scopolamine-induced learning impairment in mice involves an interaction with ?1 (sigma1) receptors. Brain Research 799, 64–77.PubMedGoogle Scholar
  164. UZUNOV, A. V., SHELINE, Y., DAVIS, J. M., RASMUSSON, A., UZUNOV, D. P., COSTA, E. & GUIDOTTI, A. (1998) Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proceedings of the National Academy of Sciences of the USA 95, 3239–3244.PubMedGoogle Scholar
  165. VALLÈ, M., MAYO, W., DARNAUDÉRY, M., CORPÉCHOT, C., YOUNG, J., KOEHL, M., LE MOAL, M., BAULIEU, E. E., ROBEL, P. & SIMON, H. (1997) Neurosteroids: Deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proceedings of the National Academy of Sciences of the USA 94, 14865–14870.PubMedGoogle Scholar
  166. VANDOREN, M. J., MATTHEWS, D. B., JANIS, G. C., GROBIN, A. C., DEVAUD, L. L. & MORROW, A. L. (2000) Neuroactive steroid 3?-hydroxy-5?-pregnane-20-one modulates electrophysiological and behavioral actions of ethanol. Journal of Neuroscience Research 20, 1982–1989.Google Scholar
  167. VOWINCKEL, E., REUTENS, D., BECHER, B., VERGE, G., EVANS, A., OWENS, T. & ANTEL, J. P. (1997) PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. Journal of Neuroscience Research 50, 345–353.PubMedGoogle Scholar
  168. WANG, M.D., WAHLSTRÖM, G. & BÄCKSTRÖM, T. (1997) The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion. Journal of Steroid Biochemistry and Molecular Biology 62, 299–306.PubMedGoogle Scholar
  169. WEAVER, C. E. J., WU, F. S., GIBBS, T. T. & FARB, D. H. (1998) Pregnenolone sulfate exacerbates NMDAinduced death of hippocampal neurons. Brain Research 803, 129–136.PubMedGoogle Scholar
  170. WEHLING, M. (1994) Nongenomic actions of steroid hormones. Trends in Endocrinolology and Metabolism 5, 347–353.Google Scholar
  171. WEST, M. J. (1999) Stereological methods for estimating the total number of neurons and synapses: Issues of precision and bias. Trends in Neurosciences 22, 51–61.PubMedGoogle Scholar
  172. WICKELGREN, I. (1996a) Is hippocampal cell death a myth? Science 271, 1229–1230.PubMedGoogle Scholar
  173. WICKELGREN, I. (1996b) For the cortex, neuron loss may be less than thought. Science 273, 48–50.PubMedGoogle Scholar
  174. WIELAND, S., BELLUZZI, J. D., STEIN, L. & LAN, N. C. (1995) Comparative behavioral characterization of the neuroactive steroids 3 alpha-OH,5 alpha-pregnan-20-one and 3 alpha-OH,5 beta-pregnan-20-one in rodents. Psychopharmacology 118, 65–71.PubMedGoogle Scholar
  175. WU, W. (1993) Expression of nitric oxide synthase in injured CNSneurons asshownby NADP-diaphorase histochemistry. Experimental Neurology 120, 153–159.PubMedGoogle Scholar
  176. YOO, A, HARRIS, J. & DUBROVSKY, B. (1996) Doseresponse study of dehydroepiandrosterone sulfate on dentate gyrus long-term potentiation. Experimental Neurology 137, 151–156.PubMedGoogle Scholar
  177. YOUNG, J., CORPÉCHOT, C., PERCHE, M., HAUG, M., BAULIEU, E. E. & ROBEL, P. (1994) Neurosteroids: Pharmacological effects of a 3?-hydroxysteroid dehydrogenase inhibitor. Endocrine Journal 2, 505–509.Google Scholar
  178. YU, W. H. (1989) Survival of motoneurons following axotomy is enhanced by lactation or by progesterone treatment. Brain Research 491, 379–382.PubMedGoogle Scholar
  179. ZWAIN, I. H. & YEN, S. S. (1999a) Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain. Endocrinology 140, 3843–3852.PubMedGoogle Scholar
  180. ZWAIN, I. H. & YEN, S. S. C. (1999b) Dehydroepiandrosterone (DHEA): Biosynthesis and metabolism in the brain. Endocrinology 140, 880–887.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Michael Schumacher
    • 1
  • Yvette Akwa
    • 1
  • Rachida Guennoun
    • 1
  • Françoise Robert
    • 1
  • Florencia Labombarda
    • 2
  • Franck Désarnaud
    • 1
  • Paul Robel
    • 1
  • Alejandro F. De Nicola
    • 2
  • Etienne-Emile Baulieu
    • 3
  1. 1.Kremlin-BicêtreFrance
  2. 2.Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Faculty of MedicineUniversity of Buenos AiresArgentina
  3. 3.Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Faculty of MedicineUniversity of Buenos Aires, Argentina

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