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Endocrine Aspects of Successful Aging: Genes, Hormones and Lifestyles pp 101–127Cite as

Aging Myelin and Cognitive Decline: a Role for Steroids

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Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

Summary

The functions of steroids go far beyond reproduction and adaptation to stress and, over the past few years, they have been shown to regulate a large number of vital neuronal and glial functions throughout the brain and in peripheral nerves. For example, progesterone exerts neuroprotective effects and plays an important role in myelination. This steroid, which is produced by the ovaries and adrenal glands and then reaches the nervous tissues via the bloodstream, can also be synthesized locally within the nervous system by neurons and glial cells. Age-associated alterations of the nervous system and cognitive decline have been related to decreased levels of steroid hormones and have been shown to be reversible by the systemic administration of steroids. It is indeed now recognized that age-related changes in the nervous system are less severe than previously thought and, most importantly, that they are partly reversible. Abnormalities, breakdown and loss of myelin sheaths are reliable markers of the aging nervous system, which correlate with both chronological age and cognitive decline. Prolonged administration of progestins over one month to old male rats has been shown to reverse the decrease in myelin protein gene expression as well as the age-related structural abnormalities of the peripheral myelin sheaths. In the brains of old rats, myelin repair is very much delayed when compared with young animals. In the cerebellar peduncle of old males, the systemic administration of progesterone for five weeks has been shown to stimulate slow remyelination after toxin-induced demyelination. Steroids that promote myelin repair and can reverse myelin sheath abnormalities thus offer a promising opportunity for preventing or treating age-dependent dysfunctions of the nervous system.

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References

  • Adinolfi AM, Yamuy J, Morales FR, Chase MH (1991) Segmental demyelination in peripheral nerves of old cats. Neurobiol Aging 12: 175–179

    Article  PubMed  CAS  Google Scholar 

  • Akwa Y, Sananès NG, Robel P, Baulieu EE, Le Goascogne C (1993) Astrocytes and neurosteroids: metabolism of pregnenolone and dehydroepiandrosterone. Regulation by cell density. J Cell Biol 121: 135–143

    Google Scholar 

  • Arlt W, Callies F, Allolio B (2000) DHEA replacement in women with adrenal insufficiency: pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition. Endocrinol Res 26: 505–511

    Article  CAS  Google Scholar 

  • Asthana S, Craft S, Baker LD, Raskind MA, Birnbaum RS, Lofgreen CP, Veith RC, Plymate SR (1999) Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer’s disease: results of a placebo-controlled, double-blind, pilot study. Psychoneuro endocrinology 24: 657–677

    Article  CAS  Google Scholar 

  • Asthana S, Baker LD, Craft S, Stanczyk FZ, Veith RC, Raskind MA, Plymate SR (2001) High-dose estradiol improves cognition for women with AD: results of a randomized study. Neurology 57: 605–612

    Article  PubMed  CAS  Google Scholar 

  • Azcoitia I, Leonelli E, Magnaghi V, Veiga S, Garcia-Segura LM, Melcangi RC (2003) Progesterone and its derivatives dihydroprogesterone and tetrahydroprogesterone reduce myelin fiber morphological abnormalities and myelin fiber loss in the sciatic nerve of aged rats. Neurobiol Aging, 24: 853–860.

    Article  PubMed  CAS  Google Scholar 

  • Balthazart J, Ball GF (1998) New insights into the regulation and function of brain estrogen synthase (aromatase). Trends Neurosci 21: 243–249

    Article  PubMed  CAS  Google Scholar 

  • Barrett-Connor E, Edelstein SL (1994) A prospective study of dehydroepiandrosterone sulfate and cognitive function in an older population: the Rancho Bernardo Study. J Am Geriatr Soc 42: 420–423

    PubMed  CAS  Google Scholar 

  • Baulieu EE (1981) Steroid hormones in the brain: several mechanisms? In: Fuxe K, Gustafsson JA, Wetterberg L (eds), Steroid hormone regulation of the brain. ( Oxford, Pergamon Press, pp 3–14

    Google Scholar 

  • Baulieu EE, Robel P, Schumacher M (1999) Neurosteroids. A new regulatory function in the nervous system. Totowa, New Jersey, Humana Press.

    Google Scholar 

  • Baulieu EE, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, Faucounau V, Girard L, Hervy MP, Latour F, Leaud MC, Mokrane A, Pitti F, Trivalle C, de Lacharriere O, Nouveau S, Rakoto A, Souberbielle JC, Raison J, Le Bouc Y, Raynaud A, Girerd X, Forette F (2000) Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA 97: 4279–4284

    Article  PubMed  CAS  Google Scholar 

  • Beck CA, Weigel NL, Moyer ML, Nordeen SK, Edwards DP (1993) The progesterone antagonist RU486 acquires agonist activity upon stimulation of cAMP signaling pathways. Proc Natl Acad Sci USA 90: 4441–4445

    Article  PubMed  CAS  Google Scholar 

  • Behl C, Skutella T, Lezoualc’h F, Post A, Widmann M, Newton CJ, Holsboer F (1997) Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Mol Pharmacol 51: 535–541

    PubMed  CAS  Google Scholar 

  • Belanger A, Candas B, DuPont A, Cusan L, Diamond P, Gomez JL, Labrie F (1994) Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. J Clin Endocrinol Metab 79: 1086–1090

    Article  PubMed  CAS  Google Scholar 

  • Bellino FL, Daynes RA, Hornsby PJ, Lavrin DH, Nestler JE (1995) Dehydroepiandrosterone (DHEA) and aging. New York, New York Academy of Sciences, vol. 774

    Google Scholar 

  • Bernardi F, Salvestroni C, Casarosa E, Nappi RE, Lanzone A, Luisi S, Purdy RH, Petraglia F, Genazzani AR (1998) Aging is associated with changes in allopregnanolone concentrations in brain, endocrine glands and serum in male rats. Eur J Endocrinol 138: 316–321

    Article  PubMed  CAS  Google Scholar 

  • Beyer C, Ivanova T, Karolczak M, Kuppers E (2002) Cell type-specificity of nonclassical estrogen signaling in the developing midbrain. J Steroid Biochem Mol Biol 81: 319

    Article  PubMed  CAS  Google Scholar 

  • Bologa L, Sharma J, Roberts E (1987) Dehydroepiandrosterone and its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures. J Neurosci Res 17: 225–234

    Article  PubMed  CAS  Google Scholar 

  • Boonyaratanakornkit V, Scott MP, Ribon V, Sherman L, Anderson SM, Mailer JL, Miller WT, Edwards DP (2001) Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Mol Cell 8: 269–280

    Article  PubMed  CAS  Google Scholar 

  • Brenner DE, Kukull WA, Stergachis A, van Belle G, Bowen JD, McCormick WC, Teri L, Larson EB (1994) Postmenopausal estrogen replacement therapy and the risk of Alzheimer’s disease: a population-based case-control study. Am J Epidemiol 140: 262–267

    PubMed  CAS  Google Scholar 

  • Buchthal F, Rosenfalck A, Behse F (1984) Sensory potentials of normal and diseased nerves. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy. Philadelphia: Saunders, pp 981–1105

    Google Scholar 

  • Burger HG, Dudley EC, Robertson DM, Dennerstein L (2002) Hormonal changes in the menopause transition. Recent Prog Horm Res 57: 257–275

    Article  PubMed  CAS  Google Scholar 

  • CaHier S, Morissette M, Grandbois M, Di Paolo T (2000) Stereospecific prevention by 17betaestradiol of MPTP-induced dopamine depletion in mice. Synapse 37: 245–251

    Article  Google Scholar 

  • Cardounel A, Regelson W, Kalimi M (1999) Dehydroepiandrosterone protects hippocampal neurons against neurotoxin-induced cell death: mechanism of action. Soc Exp Biol Med 222: 145–149

    Article  CAS  Google Scholar 

  • Carlson LE, Sherwin BB (1999) Relationships among cortisol (CRT), dehydroepiandrosteronesulfate ( DHEAS), and memory in a longitudinal study of healthy elderly men and women. Neurobiol Aging 20: 315–324

    Google Scholar 

  • Carlson LE, Sherwin BB, Chertkow MH (1999) Relationship between dehydroepiandrosterone sulfate (DHEAS) and cortisol ( CRT) plasma levels and everyday memory in Alzheimer’s disease patients compared to healthy controls. Horm Behav 35: 254–263

    Google Scholar 

  • Cascio C, Prasad VV, Lin YY, Lieberman S, Papadopoulos V (1998) Detection of P450c17independent pathways for dehydroepiandrosterone ( DHEA) biosynthesis in brain glial tumor cells. Proc Natl Acad Sci USA 95: 2862–2867

    Google Scholar 

  • Chan JR, Phillips LJ, Glaser M (1998) Glucocorticoids and progestins signal the initiation and enhance the rate of myelin formation. Proc Natl Acad Sci USA 95: 10459–10464

    Article  PubMed  CAS  Google Scholar 

  • Coirini H, Gouézou M, Liere P, Delespierre B, Pianos A, Eychenne B, Schumacher M, Guennoun R (2003) 3beta-hydroxysteroid dehydrogenase expression in rat spinal cord. Neuroscience, 113: 883–891

    Google Scholar 

  • Compagnone NA, Mellon SH (1998) Dehydroepiandrosterone: a potential signalling molecule for neocortical organization during development. Proc Natl Acad Sci USA 95: 4678–4683

    Article  PubMed  CAS  Google Scholar 

  • Corpéchot C, Robel P, Axelson M, Sjövall J, Baulieu EE (1981) Characterization and measurement of dehydroepiandrosterone sulfate in the rat brain. Proc Natl Acad Sci USA 78: 4704–4707

    Article  PubMed  Google Scholar 

  • Costa MM, Reus VI, Wolkowitz OM, Manfredi F, Lieberman M (1999) Estrogen replacement therapy and cognitive decline in memory-impaired post-menopausal women. Biol Psychiat 46: 182–188

    Article  PubMed  CAS  Google Scholar 

  • Csapo AI, Pulkkinen M (1978) Indispensability of the human corpus luteum in the maintenance of early pregnancy. Luteectomy evidence. Obstet Gynecol Sury 33: 69–81

    Google Scholar 

  • Cunningham CJ, Sinnott M, Denihan A, Rowan M, Walsh JB, O’Moore R, Coakley D, Coen RF, Lawler BA, O’Neill DD (2001) Endogenous sex hormone levels in postmenopausal women with Alzheimer’s disease. J Clin Endocrinol Metab 86: 1099–1103

    Article  PubMed  CAS  Google Scholar 

  • Demerens C, Stankoff B, Logak M, Anglade P, Allinquant B, Couraud F, Zalc B, Lubetzki C (1996) Induction of myelination in the central nervous system by electrical activity. Proc Natl Acad Sci USA 93: 9887–9892

    Article  PubMed  CAS  Google Scholar 

  • Désarnaud F, Do T, Brown AM, Lemke G, Suter U, Baulieu EE, Schumacher M (1998) Progesterone stimulates the activity of the promoters of peripheral myelin protein-22 and protein zero genes in Schwann cells. J Neurochem 71: 1765–1768

    Article  PubMed  Google Scholar 

  • Dewaegh SM, Lee VMY, Brady ST (1992) Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells. Cell 68: 451–463

    Article  CAS  Google Scholar 

  • Fajer AB, Holzbauer M, Newport HM (1971) The contribution of the adrenal gland to the total amount of progesterone produced in the female rat. J Physiol (Lond) 214: 115–126

    CAS  Google Scholar 

  • Feder HH, Resko JA, Goy RW (1968) Progesterone levels in the arterial plasma of pre-ovulatory and ovariectomized rats. J Endocrinol 41: 563–569

    Article  PubMed  CAS  Google Scholar 

  • Fernandez PA, Tang DG, Cheng L, Prochiantz A, Mudge AW, Raff MC (2000) Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve. Neuron 28: 81–90

    Article  PubMed  CAS  Google Scholar 

  • Ferrario E, Massaia M, Aimo G, di Ceva PA, Fabris F (1999) Dehydroepiandrosterone sulfate serum levels: no significance in diagnosing Alzheimer’s disease. J Endocrinol Invest 22: 81

    PubMed  CAS  Google Scholar 

  • Ferreira A, Caceres A (1991) Estrogen-enhanced neurite growth: evidence for a selective induction of Tau and stable microtubules. J Neurosci 11: 392–400

    PubMed  CAS  Google Scholar 

  • Fillenbaum GG, Hanlon JT, Landerman LR, Schmader KE (2001) Impact of estrogen use on decline in cognitive function in a representative sample of older community-resident women. Am J Epidemiol 153: 137–144

    Article  PubMed  CAS  Google Scholar 

  • Gago N, Akwa Y, Sananes N, Guennoun R, Baulieu EE, El-Etr M, Schumacher M (2001) Progesterone and the oligodendroglial lineage: stage-dependent biosynthesis and metabolism. Glia 36: 295–308

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Segura LM, Azcoitia I, Doncarlos LL (2001) Neuroprotection by estradiol. Prog Neurobiol 63: 29–60

    Article  PubMed  CAS  Google Scholar 

  • Genazzani AD, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, Nappi RE, Luisi S, Palumbo M, Purdy RH, Luisi M (2002) Circulating levels of alloprenanolone in humans: gender, age and endocrine influences. J Clin Endocrinol Metab 83: 2099–2103

    Article  Google Scholar 

  • Gilson J, Blakemore WF (1993) Failure of remyelination in areas of demyelination produced in the spinal cord of old rats. Neuropathol Appl Neurobiol 19: 173–181

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Isla T, Price JL, McKeel DW, Morris JC, Growdon JH, Hyman BT (1996) Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. J Neurosci 16: 4491–4500

    PubMed  CAS  Google Scholar 

  • Goodman Y, Bruce AJ, Cheng B, Mattson MP (1996) Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem 66: 1836–1844

    Article  PubMed  CAS  Google Scholar 

  • Goujet-Zalc C, Babinet C, Monge M, Timsit S, Gabon 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. Eur J Neurosci 5: 624–632

    Article  PubMed  CAS  Google Scholar 

  • Gould E, Tanapat P, Rydel T, Hastings N (2000) Regulation of hippocampal neurogenesis in adulthood. Biol Psychiat 48: 715–720

    Article  PubMed  CAS  Google Scholar 

  • Green PS, Perez EJ, Calloway T, Simpkins JW (2000) Estradiol attenuation of beta-amyloid-induced toxicity: a comparison of MTT and calcein AM assays. J Neurocytol 29: 419–423

    Article  PubMed  CAS  Google Scholar 

  • Grover-Johnson N, Spencer PS (1981) Peripheral nerve abnormalities in aging rats. J Neuropathol Exp Neurol 40: 155–165

    Article  PubMed  CAS  Google Scholar 

  • Guennoun R, Fiddes RJ, Gouézou M, Lombès M, Baulieu EE (1995) A key enzyme in the biosynthesis of neurosteroids, 313-hydroxysteroid dehydrogenase/45–44-isomerase (313HSD), is expressed in rat brain. Mol Brain Res 30: 287–300

    Article  PubMed  CAS  Google Scholar 

  • Guennoun R, Schumacher M, Robert F, Delespierre B, Gouézou M, Eychenne B, Akwa Y, Robel P, Baulieu EE (1997) Neurosteroids: expression of functional313-hydroxysteroid dehydrogenase by rat sensory neurons and Schwann cells. Eur J Neurosci 9: 2236–2247

    Article  PubMed  CAS  Google Scholar 

  • Gutai JP, Meyer WJ, Kowarski AA, Migeon CJ (1977) Twenty-four hour integrated concentrations of progesterone, 17-hydroxyprogesterone and cortisol in normal male subjects. J Clin Endocrinol Metab 44: 116–120

    Article  PubMed  CAS  Google Scholar 

  • Henderson VW, Paganini-Hill A, Emanuel CK, Dunn ME, Buckwalter JG (1994) Estrogen replacement therapy in older women. Comparisons between Alzheimer’s disease cases and nondemented control subjects. Arch Neurol 51: 896–900

    Google Scholar 

  • Henderson VW, Paganini-Hill A, Miller BL, Elbe RJ, Reyes PF, Shoupe D, McCleary CA, Klein RA, Hake AM, Farlow MR (2000) Estrogen for Alzheimer’s disease in women: randomized, double-blind, placebo-controlled trial. Neurology 54: 295–301

    Article  PubMed  CAS  Google Scholar 

  • Herbert J (1995) The age of dehydroepiandrosterone. Lancet 345: 1193–1194

    Article  PubMed  CAS  Google Scholar 

  • Hildebrand C, Bowe CM, Remahl IN (1994) Myelination and myelin sheath remodelling in normal and pathological PNS nerve fibers. Prog Neurobiol 43: 85–141

    Article  PubMed  CAS  Google Scholar 

  • Hinks GL, Franklin RIM (2000) Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats. Mol Cell Neurosci 16: 542–556

    Article  PubMed  CAS  Google Scholar 

  • Holzbauer M, Newport HM, Birmingham MK, Traikov H (1969) Secretion of pregn-4-ene-3,20dione (progesterone) in vivo by the adrenal gland of the rat. Nature 221: 572–573

    Article  PubMed  CAS  Google Scholar 

  • Ibanez C, Shields SA, El Etr M, Leonelli E, Magnaghi V, Li WW, Sim FJ, Baulieu EE, Melcangi RC, Schumacher M, Franklin RJ (2003a) Steroids and the reversal of age-associated changes in myelination and remyelination. Prog Neurobiol, in press.

    Google Scholar 

  • Ibanez C, Shields SA, Liere P, el-Etr M, Baulieu EE, Schumacher M, Franklin RJM (2003b) Systemic progesterone administration results in a partial reversal of the age-associated decline in CNS remyelination following toxin-induced demyelination in male rats. Neuropathol Appl Neurobiol, in press.

    Google Scholar 

  • Jacobs DM, Tang MX, Stern Y, Sano M, Marder K, Bell KL, Schofield P, Dooneief G, Gurland B, Mayeux R (1998) Cognitive function in nondemented older women who took estrogen after menopause. Neurology 50: 368–373

    Article  PubMed  CAS  Google Scholar 

  • Jiang N, Chopp M, Stein DG, Feldblum S (1996) Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats. Brain Res 735: 101–107

    Article  PubMed  CAS  Google Scholar 

  • Jones SI (1993) Visual evoked potentials after optic neuritis. J Neurol 240: 489–494.

    Article  PubMed  CAS  Google Scholar 

  • Jung-Testas I, Hu ZY, Baulieu EE, Robel P (1989) Neurosteroids: Biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells. Endocrinology 125: 2083–2091

    Google Scholar 

  • Jung-Testas I, Renoir JM, Gasc JM, Baulieu EE (1991) Estrogen-inducible progesterone receptor in primary cultures of rat glial cells. Exp Cell Res 193: 12–19

    Article  PubMed  CAS  Google Scholar 

  • Jung-Testas I, Schumacher M, Robel P, Baulieu EE (1996a) Demonstration of progesterone receptors in rat Schwann cells. J Steroid Biochem Mol Biol 58: 77–82

    Article  PubMed  CAS  Google Scholar 

  • Jung-Testas I, Schumacher M, Robel P, Baulieu EE (1996b) The neurosteroid progesterone increases the expression of myelin proteins ( MBP and CNPase) in rat oligodendrocytes in primary culture. Cell Mol Neurobiol 16: 439–443

    Google Scholar 

  • Kalimi M, Regelson W (1990) The biological role of dehydroepiandrosterone. Berlin, Walter de Gruyter

    Google Scholar 

  • Kalmijn S, Launer LJ, Stolk RP, De Jong FH, Pols HA, Hofman A, Breteler MM, Lamberts SW (1998) A prospective study on cortisol, dehydroepiandrosterone sulfate, and cognitive function in the elderly. J Clin Endocrinol Metab 83: 3487–3492

    Article  PubMed  CAS  Google Scholar 

  • Kanda T, Tsukagoshi H, Oda M, Miyamoto K, Tanabe H (1991) Morphological changes in unmyelinated fibers in the sural nerve with age. Brain 114: 585–599

    Article  PubMed  Google Scholar 

  • Karishma KK, Herbert J (2002) Dehydroepiandrosterone ( DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression. Eur J Neurosci 16: 445–453

    Google Scholar 

  • Kawas C, Resnick S, Morrison A, Brookmeyer R, Corrada M, Zonderman A, Bacal C, Lingle DD, Metter E (1997) A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology 48: 1517–1521

    Article  PubMed  CAS  Google Scholar 

  • Key TJ (2000) Progestins in postmenopausal women: epidemiological data on relationships with endometrial and breast cancer risk. In: Sitruk-Ware R, Mishell DR (eds) Progestins and antiprogestins in clinical practice New York: Marcel Dekker, pp 279–287

    Google Scholar 

  • Khaw KT (1992) Epidemiology of the menopause. Br Med Bull 48: 249–261

    PubMed  CAS  Google Scholar 

  • KimonidesVG,SpilantiniMG,SofroniewMV,FawcettJW,Herbert J (1999) Dehydroepiandrosterone antagonizes the neurotoxic effects of corticosterone and translocation of stress-activated protein kinase 3 in hippocampal primary cultures. Neuroscience 89: 429–436

    Article  Google Scholar 

  • Knox CA, Kokmen E, Dyck PJ (1989) Morphometric alteration of rat myelinated fibers with aging. J Neuropathol Exp Neurol 48: 119–139

    Article  PubMed  CAS  Google Scholar 

  • Koenig H, Schumacher M, Ferzaz B, Do Thi AN, Ressouches A, Guennoun R, Jung-Testas I, Robel P, Akwa Y, Baulieu EE (1995) Progesterone synthesis and myelin formation by Schwann cells. Science 268: 1500–1503

    Article  PubMed  CAS  Google Scholar 

  • Koski CL, Max SR (1980) Comparison of the protein composition of myelin of motor and sensory nerves. J Neurochem 34: 449–452

    Article  PubMed  CAS  Google Scholar 

  • Kousteni S, Bellido T, Plotkin LI, Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC (2001) Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104: 719–730

    PubMed  CAS  Google Scholar 

  • Labrie F, Bélanger A, Cusan L, Candas B (1997) Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology. J Clin Endocrinol Metab 82: 2403–2409

    Article  PubMed  CAS  Google Scholar 

  • Lambert JJ, Belleli D, Shepherd SE, Pistis M, Peters JA (1999) The selective interaction of neurosteroids with the GABAA receptor. In: Baulieu EE, Robel P, Schumacher M (eds), Neurosteroids. A new regulatory function in the nervous system. (Totowa, New Jersey, Humana Press, pp 125–142

    Google Scholar 

  • Lamberts SW, van den Beld AW, van der Lely AJ (1997) The endocrinology of aging. Science 278: 419–424

    Article  PubMed  CAS  Google Scholar 

  • Lascelles RG, Thomas PK (1966) Changes due to age in internodal length in the sural nerve in man. J Neurol Neurosurg Psychiat 29: 40–44

    Article  PubMed  CAS  Google Scholar 

  • Laughlin GA, Barrett-Connor E (2000) Sexual dimorphism in the influence of advanced aging on adrenal hormone levels: the Rancho Bernardo Study. J Clin Endocrinol Metab 85: 3561–3568

    Article  PubMed  CAS  Google Scholar 

  • Leblhuber F, Neubauer C, Peichl M, Reisecker F, Steinparz FX, Windhager E, Dienstl E (1993) Age and sex differences of dehydroepiandrosterone sulfate (DHEAS) and cortisol (CRT) plasma levels in normal controls and Alzheimer’s disease ( AD ). Psychopharmacology 111: 23–26

    Google Scholar 

  • Le Goascogne C, Robel P, Gouézou M, Sananès N, Baulieu EE, Waterman M (1987) Neurosteroids: cytochrome P450scc in rat brain. Science 237: 1212–1215

    Article  PubMed  Google Scholar 

  • Le Goascogne C, Gouézou M, Robel P, Defaye G, Chambaz E, Waterman MR, Baulieu EE (1989) The cholesterol side-chain cleavage complex in human brain white matter. J Neuroendocrinol 1: 153–156

    Article  PubMed  CAS  Google Scholar 

  • Lee SJ, McEwen BS (2001) Neurotrophic and neuroprotective actions of estrogens and their therapeutic implications. Annu Rev Pharmacol Toxicol 41: 569–591

    Article  PubMed  CAS  Google Scholar 

  • Legrain S, Berr C, Frenoy N, Gourlet V, Debuire B, Baulieu EE (1995) Dehydroepiandrosterone sulfate in a long-term care aged population. Gerontology 41: 343–351

    Article  PubMed  CAS  Google Scholar 

  • Lemke G (1993) The molecular genetics of myelination: an update. Glia 7: 263–271

    Article  PubMed  CAS  Google Scholar 

  • Lorenzo A, Diaz H, Carrer H, Caceres A (1992) Amygdala neurons in vitro–neurite growth and effects of estradiol. J Neurosci Res 33: 418–435

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, De Leon M, de Santi S, Convit A, Tarshish C, Nair NP, Thakur M, McEwen BS, Hauger RL, Meaney MJ (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nature Neurosci 1: 69–73

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, Nair NP, Briere S, Maheu F, Tu MT, Lemay M, McEwen BS, Meaney MJ (1999) Increased cortisol levels and impaired cognition in human aging: implication for depression and dementia in later life. Rev Neurosci 10: 117–139

    PubMed  CAS  Google Scholar 

  • Magnaghi V, Cavarretta I, Zucchi I, Susani L, Rupprecht R, Hermann B, Martini L, Melcangi RC (1999) Po gene expression is modulated by androgens in the sciatic nerve of adult male rats. Mol Brain Res 70: 36–44

    Article  PubMed  CAS  Google Scholar 

  • Magnaghi V, Cavarretta I, Galbiati M, Martini L, Melcangi RC (2001) Neuroactive steroids and peripheral myelin proteins. Brain Res Rev 37: 360–371

    Article  PubMed  CAS  Google Scholar 

  • Maisonobe T, Hauw JJ (1997) Changes in the peripheral nervous system. In: Dani SU, Hori A, Walter GF (eds) Principles of neural aging ( Amsterdam, Elsevier, pp 304–316

    Google Scholar 

  • Mani SK, O’Malley BW (2002) Mechanisms of progesterone receptor action in the brain. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT (eds) Hormones, brain and behavior. Volume 3. Amsterdam, Academic Press, pp 643–682

    Chapter  Google Scholar 

  • Manly JJ, Merchant CA, Jacobs DM, Small SA, Bell K, Ferin M, Mayeux R (2000) Endogenous estrogen levels and Alzheimer’s disease among postmenopausal women. Neurology 54: 833–837.

    Article  PubMed  CAS  Google Scholar 

  • Marchionni MA, Cannella B, Hoban C, Gao YL, Garcia A, Lawson D, Happel E, Noel F, Tofilon P, Gwynne D, Raine CS (1999) Neuregulin in neuron/glial interactions in the central nervous system. GGF2 diminishes autoimmune demyelination, promotes oligodendrocyte progenitor expansion, and enhances remyelination. Adv Exp Med Biol 468: 283–295

    Article  PubMed  CAS  Google Scholar 

  • Maurice T, Junien JL, Privat A (1997) Dehydroepiandrosterone sulfate attenuates dizocilpine- induced learning impairment in mice via sigma 1-receptors. Behav Brain Res 83: 159–164

    Article  PubMed  CAS  Google Scholar 

  • Maurice T, Su TP, Privat A (1998) Sigmal (sigma 1) receptor agonists and neurosteroids attenuate B25–35-amyloid peptide-induced amnesia in mice through a common mechanism. Neuroscience 83: 413–428

    Article  PubMed  CAS  Google Scholar 

  • Mayo W, Vallée M, Darnaudéry M, Le Moal M (1999) Neurosteroids: behavioral studies. In: Baulieu EE, Robel P, Schumacher M (eds) Neurosteroids. A new regulatory function in the nervous system. (Totowa, New Jersey, Humana Press, pp 317–336

    Google Scholar 

  • Mazat L, Lafont S, Debuire B, Tessier JF, Dartigues JF, Baulieu EE (2001) Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: relationship,to gender, subjective health, smoking habits, and 10-year mortality. Proc Natl Acad Sci USA 98: 81458150

    Google Scholar 

  • McEwen BS, Sapolsky RM (1995) Stress and cognitive function. Curr Opin Neurobiol 5: 205–216

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS, Alves SE (1999) Estrogen actions in the central nervous system. Endocrinol Rev 20: 279–307

    Article  CAS  Google Scholar 

  • McEwen BS, De Leon MJ, Lupien SJ, Meaney MJ (1999) Corticosteroids, the aging brain and cognition. Trends Endocrinol Metab 10: 92–96

    Article  PubMed  CAS  Google Scholar 

  • McIntosh MK, Pan JS, Berdanier CD (1993) In vitro studies on the effects of dehydroepiandrosterone and corticosterone on hepatic-steroid receptor-binding and mitochondrial respiration. Comp Biochem Physiol 104: 147–153

    Article  CAS  Google Scholar 

  • McKenna NJ, Lanz RB, O’Malley BW (1999) Nuclear receptor coregulators: cellular and molecular biology. Endocrinol Rev 20: 321–344

    Article  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Ballabio M, Castano P, Poletti A, Milani S, Martini L (1988) Ontogenic development of the 5a-reductase in the rat brain: cerebral cortex, hypothalamus, purified myelin and isolated oligodendrocytes. Dev Brain Res 44: 181–188

    Article  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Ballabio M, Poletti A, Martini L (1990) Testosterone metabolism in peripheral nerves: presence of the 5a-reductase-3ß-hydroxysteroid-dehydrogenase enzymatic system in the sciatic nerve of adult and aged rats. J Steroid Biochem 35: 145–148

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Celotti F, Castano P, Martini L (1992) Is the 5a-reductase-3a-hydroxysteroid dehydrogenase complex associated with the myelin in the peripheral nervous system of young and old male rats ? Endocrine Res 26: 119–125

    CAS  Google Scholar 

  • Melcangi RC, Celotti F, Martini L (1994a) Neurons influence the metabolism of testosterone in cultured astrocytes via hormonal signals. Endocrine J 2: 709–713

    CAS  Google Scholar 

  • Melcangi RC, Celotti F, Martini L (1994b) Progesterone 5a-reduction in neuronal and in different types of glial cell cultures: type 1 and type 2 astrocytes and oligodendrocytes. Brain Res 639: 202–206

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Magnaghi V, Cavarretta I, Riva MA, Piva F, Martini L (1998a) Effects of steroid hormones on gene expression of glial markers in the central and peripheral nervous system: variations induced by aging. Exp Gerontol 33: 827–836

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Magnaghi V, Cavarretta I, Martini L, Piva F (1998b) Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives. Neuroscience 85: 569–578

    Google Scholar 

  • Melcangi RC, Magnaghi V, Cavarretta I, Zucchi I, Bovolin P, D’Urso D, Martini L (1999) Progesterone derivatives are able to influence peripheral myelin protein 22 and PO gene expression: possible mechanisms of action. J Neurosci Res 56: 349–357

    Article  PubMed  CAS  Google Scholar 

  • Melcangi RC, Magnaghi V, Martini L (2000) Aging in peripheral nerves: regulation of myelin protein genes by steroid hormones. Prog Neurobiol 60: 291–308.

    Article  PubMed  CAS  Google Scholar 

  • Mellon SH, Griffin LD, Compagnone NA (2001) Biosynthesis and action of neurosteroids. Brain Res Rev 37: 3–12

    Article  PubMed  CAS  Google Scholar 

  • Mensah-Nyagan AG, Feuifloley M, Dupont E, Do-Rego JL, Leboulenger F, Pelletier G, Vaudry H (1994) Immunocytochemical localization and biological activity of 3ß-hydroxysteroid dehydrogenase in the central nervous system of the frog. J Neurosci 14: 7306–7318

    PubMed  CAS  Google Scholar 

  • Mensah-Nyagan AG, Do-Rego JL, Beaujean D, Luu-The V, Pelletier G, Vaudry H (1999) Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system. Pharmacol Rev 51: 63–81

    PubMed  CAS  Google Scholar 

  • Messing A, Behringer RR, Hammang JP, Palmiter RD, Brinster RL, Lemke G (1992) Po promoter directs expression of reporter and toxin genes to Schwann cells of transgenic mice. Neuron 8: 507–520

    Article  PubMed  CAS  Google Scholar 

  • Morales AJ, Nolan JJ, Nelson JC, Yen SSC (1994) Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 78: 1360–1367

    Article  PubMed  CAS  Google Scholar 

  • Morales AJ, Haubrich RH, Hwang JY,Asakura H, Yen SS (1998) The effect of six months treatment with 100 mg daily dose of dehydroepiandrosterone ( DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol 49: 421–432

    Google Scholar 

  • Morfin R, Young J, Corpéchot C, Egestad B, Sjövall J, Baulieu EE (1992) Neurosteroids: pregnenolone in human sciatic nerves. Proc Natl Acad Sci USA 89: 6790–6793

    Article  PubMed  CAS  Google Scholar 

  • Morley JE, Kaiser F, Raum WJ, Perry HM, Flood JF, Jensen J, Silver AJ, Roberts E (1997) Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA 94: 7537–7542

    Article  PubMed  CAS  Google Scholar 

  • Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, Grundman M, Thomas R, Thal LJ (2000) Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. JAMA 283: 1007–1015

    Article  PubMed  CAS  Google Scholar 

  • Murialdo G, Nobili F, Rollero A, Gianelli MV, Copello F, Rodriguez G, Polleri A (2000) Hippocampal perfusion and pituitary-adrenal axis in Alzheimer’s disease. Neuropsychobiology 42: 51–57

    Article  PubMed  CAS  Google Scholar 

  • Nafziger AN, Bowlin SJ, Jenkins PL, Pearson TA, Melcangi RC, Celotti F, Ballabio M, Poletti A, Castano P, Martini L, Biegon A, Fischette CT, Rainbow TC, McEwen BS (1998) Longitudinal changes in dehydroepiandrosterone concentrations in men and women. J Lab Clin Med 131: 316–323

    Article  PubMed  CAS  Google Scholar 

  • Notterpek L, Snipes GJ, Shooter EM (1999) Temporal expression pattern of peripheral myelin protein 22 during in vivo and in vitro myelination. Glia 25: 358–369

    Article  PubMed  CAS  Google Scholar 

  • Nichols NR, Zieba M, Bye N (2001) Do glucocorticoids contribute to brain aging? Brain Res Rev 37: 273–286

    Article  PubMed  CAS  Google Scholar 

  • Nordeen SK, Bona BJ, Moyer ML (1993) Latent agonist activity of the steroid antagonist, RU486, is unmasked in cells treated with activators of protein kinase A. Mol Endocrinol 7: 731–742

    Article  PubMed  CAS  Google Scholar 

  • Orentreich N, Brind JL, Rizer RL, Vogelman JH (1984) Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 59: 551–555

    Article  PubMed  CAS  Google Scholar 

  • Paganini-Hill A, Henderson VW (1994) Estrogen deficiency and risk of Alzheimer’s disease in women. Am J Epidemiol 140: 256–261

    PubMed  CAS  Google Scholar 

  • Paganini-Hill A, Henderson VW (1996) Estrogen replacement therapy and risk of Alzheimer’s disease. Arch Intern Med 156: 2213–2217.

    Article  PubMed  CAS  Google Scholar 

  • Papadopoulos V, Brown AS (1995) Role of the peripheral-type benzodiazepine receptor and the polypeptide diazepam binding inhibitor in steroidogenesis. J Steroid Biochem Mol Biol 53: 103–110

    Article  PubMed  CAS  Google Scholar 

  • Papadopoulos V, Guarneri P, Krueger KE, Guidotti A, Costa E (1992) Pregnenolone biosynthesis in C6–2B glioma cell mitochondria–regulation by a mitochondrial diazepam binding inhibitor receptor. Proc Natl Acad Sci USA 89: 5113–5117

    Article  PubMed  CAS  Google Scholar 

  • Peters A (1996) Age-related changes in oligodendrocytes in monkey cerebral cortex. J Comp Neurol 371: 153–163

    Article  PubMed  CAS  Google Scholar 

  • Peters A (2002) Structural changes in the normally aging cerebral cortex of primates. Prog Brain Res 136: 455–465

    Article  PubMed  Google Scholar 

  • Peters A, Rosene DL, Moss MB, Kemper TL, Abraham CR, Tigges J, Albert MS (1996) Neurobiological bases of age-related cognitive decline in the rhesus monkey. J Neuropathol Exp Neurol 55: 861–874

    PubMed  CAS  Google Scholar 

  • Peters A, Morrison JH, Rosene DL, Hyman BT (1998) Feature article: are neurons lost from the primate cerebral cortex during normal aging? Cereb Cortex 8: 295–300

    Article  PubMed  CAS  Google Scholar 

  • Peters A, Moss MB, Sethares C (2000) Effects of aging on myelinated nerve fibers in monkey primary visual cortex. J Comp Neurol 419: 364–376

    Article  PubMed  CAS  Google Scholar 

  • Peters A, Sethares C, Killiany RJ (2001) Effects of age on the thickness of myelin sheaths in monkey primary visual cortex. J Comp Neurol 435: 241–248

    Article  PubMed  CAS  Google Scholar 

  • Phillips SM, Sherwin BB (1992) Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology 17: 485–495

    Article  PubMed  CAS  Google Scholar 

  • Pike MC, Ross RK (2000) Progestins and menopause: epidemiological studies of risks of endometrial and breast cancer. Steroids 65: 659–664

    Article  PubMed  CAS  Google Scholar 

  • Pittella JEH (1997) Changes in white matter. In: Dani SU, Hori A, Walter GF (eds) Principles of neural aging. Amsterdam, Elsevier, pp 285–295

    Google Scholar 

  • Ravaglia G, Forti P, Maioli F, Boschi F, Bernardi M, Pratelli L, Pizzoferrato A, Gasbarrini G (1996) The relationship of dehydroepiandrosterone sulfate (DHEAS) to endocrine-metabolic parameters and functional status in the oldest-old. Results from an Italian study on healthy free-living over-ninety-year-olds. J Clin Endocrinol Metab 81: 1173–1178

    Google Scholar 

  • Razandi M, Oh P, Pedram A, Schnitzer J, Levin ER (2002) ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions. Mol Endocrinol 16: 100–115

    Article  PubMed  CAS  Google Scholar 

  • Resko JA (1969) Endocrine control of adrenal progesterone secretion in the ovariectomized rat. Science 164: 70–71

    Article  PubMed  CAS  Google Scholar 

  • Resnick SM, Maki PM, Golski S, Kraut MA, Zonderman AB (1998) Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance. Horm Behav 34: 171–182

    Article  PubMed  CAS  Google Scholar 

  • Reynolds ML, Woolf CJ (1993) Reciprocal Schwann cell-axon interactions. Curr Opin Neurobiol 3: 683–693

    Article  PubMed  CAS  Google Scholar 

  • Robel P, Schumacher M, Baulieu EE (1999) Neurosteroids: from definition and biochemistry to physiological function. In: Baulieu EE, Robel P, Schumacher M)eds) Neurosteroids. A new regulatory function in the nervous system. ( Totowa, Humana Press, pp 1–25

    Google Scholar 

  • Robert F, Guennoun R, Desarnaud F, Do-Thi A, Benmessahel Y, Baulieu EE, Schumacher M (2001) Synthesis of progesterone in Schwann cells: regulation by sensory neurons. Eur J Neurosci 13: 916–924

    Article  PubMed  CAS  Google Scholar 

  • Roof RL, Duvdevani R, Stein DG (1993) Gender influences outcome of brain injury–progesterone plays a protective role. Brain Res 607: 333–336

    Article  PubMed  CAS  Google Scholar 

  • Roof RL, Duvdevani R, Braswell L, Stein DG (1994) Progesterone facilitates cognitive recovery and reduces secondary neuronal loss caused by cortical contusion injury in male rats. Exp Neurol 129: 64–69

    Article  PubMed  CAS  Google Scholar 

  • Rowe JW, Kahn RL (1997) Successful aging. Gerontology 37: 433–440

    Article  CAS  Google Scholar 

  • Rupprecht R, di M, Hermann B, Strohle A, Lancel M, Romeo E, Holsboer F (2001) Neuroactive steroids: molecular mechanisms of action and implications for neuropsychopharmacology. Brain Res Rev 37: 59–67

    Article  PubMed  CAS  Google Scholar 

  • Sandell JH, Peters A (2001) Effects of age on nerve fibers in the rhesus monkey optic nerve. J Comp Neurol 429: 541–553

    Article  PubMed  CAS  Google Scholar 

  • Sanne JL, Krueger KE (1995) Expression of cytochrome P450 side-chain cleavage enzyme and 3ß-hydroxysteroid dehydrogenase in the rat central nervous system: a study by polymerase chain reaction and in situ hybridization. J Neurochem 65: 528–536

    Article  PubMed  CAS  Google Scholar 

  • Sato A, Sato Y, Suzuki H (1985) Aging effects on conduction velocities of myelinated and unmyelinated fibers of peripheral nerves. Neurosci Lett 53: 15–20.

    Article  PubMed  CAS  Google Scholar 

  • Schaeffer C, Aron C (1987) Stress-related effects on the secretion of progesterone by the adrenals in castrated male rats presented to stimulus males. Involvement of oestrogen. Acta Endocrinol 114: 440–445

    Google Scholar 

  • Schmidt BM, Gerdes D, Feuring M, Falkenstein E, Christ M, Wehling M (2000) Rapid, nongenomic steroid actions: A new age? Front Neuroendocrinol 21: 57–94

    Article  PubMed  CAS  Google Scholar 

  • Schonknecht P, Pantel J, Klinga K, Jensen M, Hartmann T, von Bergmann K, Beyreuther K, Schroder J (2001) Reduced cerebrospinal fluid estradiol levels are associated with increased beta-amyloid levels in female patients with Alzheimer’s disease. Neurosci Lett 307: 83–85

    Article  Google Scholar 

  • Schumacher M, Robert F (2002) Progesterone: synthesis, metabolism, mechanisms of action, and effects in the nervous system. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT (eds) Hormones, brain and behavior. Volume 3. Amsterdam, Academic Press, pp 683–745

    Chapter  Google Scholar 

  • Schumacher M, Coirini H, Robert F, Guennoun R, el-Etr M (1999) Genomic and membrane actions of progesterone: implications for reproductive physiology and behavior. Behav Brain Res 105: 37–52

    Article  PubMed  CAS  Google Scholar 

  • Schumacher M, Guennoun R, Mercier G, Desarnaud F, Lacor P, Benavides J, Ferzaz B, Robert F, Baulieu EE (2001) Progesterone synthesis and myelin formation in peripheral nerves. Brain Res Rev 37: 343–359

    Article  PubMed  CAS  Google Scholar 

  • Shields SA, Gilson JM, Blakemore WF, Franklin RJ (1999) Remyelination occurs as extensively but more slowly in old rats compared to young rats following gliotoxin-induced CNS demyelination. Glia 28: 77–83

    Article  PubMed  CAS  Google Scholar 

  • Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001) Neurogenesis in the adult is involved in the formation of trace memories. Nature 410: 372–376

    Article  PubMed  CAS  Google Scholar 

  • Sih R, Morley JE, Kaiser FE, Perry HM, Patrick P, Ross C (1997) Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 82: 1661–1667

    Article  PubMed  CAS  Google Scholar 

  • Sim FJ, Zhao C, Penderis J, Franklin RJM (2002) The age-related decrease in CNS remyelination efficiency is attribuable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci 22: 2451–2459

    PubMed  CAS  Google Scholar 

  • Sitruk-Ware R (2000a) Progestins in hormonal replacement therapy and cardiovascular risk. In: (Sitruk-Ware R, Mishell DR (eds) Progestins and antiprogestins in clinical practice New York, Marcel Dekker, pp 289–304

    Google Scholar 

  • Sitruk-Ware R (2000b) Progestins in hormonal replacement therapy and prevention of endometrial disease. In: Sitruk-Ware R, Mishell DR (eds) Progestins and antiprogestins in clinical practice ( New York, Marcel Dekker, pp 269–277

    Google Scholar 

  • Sitruk-Ware R (2002) Progestogens in hormonal replacement therapy: new molecules, risks, and benefits. Menopause 9: 6–15

    Article  PubMed  Google Scholar 

  • Smith YR, Giordani B, Lajiness 0, Zubieta JK (2001) Long-term estrogen replacement is associated with improved nonverbal memory and attentional measures in postmenopausal women. Fertil Steril 76: 1101–1107

    Article  PubMed  CAS  Google Scholar 

  • Snipes GJ, Suter U (1994) Signaling pathways mediating axon-Schwann cell interactions. Trends Neurosci 17: 399–401

    Article  PubMed  CAS  Google Scholar 

  • Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, Dlewati A, Staley J, Santanna J, Kapoor SC, Attie MF, Haddad JG, Strom BL (1999a) Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 84: 1966–1972

    Article  PubMed  CAS  Google Scholar 

  • Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL (1999b) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84: 2647–2653

    Article  PubMed  CAS  Google Scholar 

  • Sowers MR, La Pietra MT (1995) Menopause: its epidemiology and potential association with chronic diseases. Epidemiol Res 17: 287–302

    CAS  Google Scholar 

  • Stein DG (2001) Brain damage, sex hormones and recovery: a new role for progesterone and estrogen? Trends Neurosci 24: 386–391

    Article  PubMed  CAS  Google Scholar 

  • Stevens JC, Lofgren EP, Dyck PD (1973) Histometric evaluation of branches of peroneal nerve: technique for combined biopsy of muscle nerve and cutaneous nerve. Brain Res 52: 37–59.

    Article  PubMed  CAS  Google Scholar 

  • Strömstedt M, Waterman MR (1995) Messenger RNAs encoding steroidogenic enzymes are expressed in rodent brain. Mol Brain Res 34: 75–88

    Article  PubMed  Google Scholar 

  • Suter, U. Snipes GJ (1998) Biology and genetics of hereditary motor and sensory neuropathies. Annu Rev Neurosci 18: 45–75

    Article  Google Scholar 

  • Suter U, Nave KA (1999) Transgenic mouse models of CMT1A and HNPP. Ann NY Acad Sci 883: 247–253

    Article  PubMed  CAS  Google Scholar 

  • Tanzer L, Jones KJ (1997) Gonadal steroid regulation of hamster facial nerve regeneration: effects of dihydrotestosterone and estradiol. Exp Neurol 146: 258–264

    Article  PubMed  CAS  Google Scholar 

  • Tenover JS (1992) Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 75: 1092–1098

    Article  PubMed  CAS  Google Scholar 

  • Thomas AJ, Nockels RP, Pan HQ, Shaffrey CI, Chopp M (1999) Progesterone is neuroprotective after acute experimental spinal cord trauma in rats. Spine 24: 2134–2138

    Article  PubMed  CAS  Google Scholar 

  • Thomas PK, King RHM, Sharma AK (1980) Changes with age in the peripheral nerves of the rat. Acta Neuropathol (Berlin) 52: 417–428

    Article  Google Scholar 

  • Tigges J, Herndon JG, Rosene DL (1996) Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys. Acta Anat (Basel) 157: 63–72

    Article  CAS  Google Scholar 

  • Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi ABY, Seitanidou T, Babinet C, Charnay P (1994) Krox-20 controls myelination in the peripheral nervous system. Nature 371: 796–799

    Article  PubMed  CAS  Google Scholar 

  • Tsutsui K, Ukena K, Usui M, Sakamoto H, Takase M (2000) Novel brain function: biosynthesis and actions of neurosteroids in neurons. Neurosci Res 36: 261–273

    Article  PubMed  CAS  Google Scholar 

  • Uchida Y, Tomonaga M, Nomura K (1986) Age-related changes of myelin proteins in the rat peripheral nervous system. J Neurochem 46: 1376–1381

    Article  PubMed  CAS  Google Scholar 

  • Ukena K, Kohchi C, Tsutsui K (1999) Expression and activity of 3beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase in the rat Purkinje neuron during neonatal life. Endocrinology 140: 805–813

    Article  PubMed  CAS  Google Scholar 

  • Urani A, Privat A, Maurice T (1998) The modulation by neurosteroids of the scopolamine-induced learning impairment in mice involves an interaction with sigmal (sigma 1) receptors. Brain Res 799: 64–77

    Article  PubMed  CAS  Google Scholar 

  • Vallée M, Mayo W, Darnaudery M, Corpéchot C, Young J, Koehl M, Le Moal M, Baulieu EE, Robel P, Simon H (1997) Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci USA 94: 14865–14870

    Article  PubMed  Google Scholar 

  • van den Beld AW, Lamberts SWJ (2002) Endocrine aspects of healthy ageing in men. In: Chadwick DJ, Goode JA (eds) Novartis Foundation Symposium 242: Endocrine facets of ageing. ( Chichester, UK, John Wiley, pp 3–16

    Google Scholar 

  • van Niekerk JK, Huppert FA, Herbert J (2001) Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation. Psychoneuro endocrinology 26: 591–612

    Article  Google Scholar 

  • Vermeulen A (1991) Clinical review 24: androgens in the aging male. J Clin Endocrinol Metab 73: 221–224

    Article  PubMed  CAS  Google Scholar 

  • Vermeulen A, Verdonck L (1976) Radioimmunoassay of 17beta-hydroxy-5alpha-androstan-3one, 4-androstene-3,17-dione, dehydroepiandrosterone, 17-hydroxyprogesterone and progesterone and its application to the human male plasma. J Steroid Biochem 7: 1–10

    Article  PubMed  CAS  Google Scholar 

  • Wang PN, Liao SQ, Liu RS, Liu CY, Chao HT, Lu SR, Yu HY, Wang SJ, Liu HC (2000) Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology 54: 2061–2066

    Article  PubMed  CAS  Google Scholar 

  • West MJ, Kawas CH, Martin LJ, Troncoso JC (2000) The CA1 region of the human hippocampus is a hot spot in Alzheimer’s disease. Ann NY Acad Sci 908: 255–259

    Article  PubMed  CAS  Google Scholar 

  • Wickelgren I (1996a) For the cortex, neuron loss may be less than thought. Science 273: 48–50

    Article  PubMed  CAS  Google Scholar 

  • Wickelgren I (1996b) Is hippocampal cell death a myth ? Science 271: 1229–1230

    Article  PubMed  CAS  Google Scholar 

  • Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL (1999) Neuroendocrine influences and repercussions of the menopause. Endocrinol Rev 20: 243–248

    Article  CAS  Google Scholar 

  • Wise PM, Dubal DB, Wilson ME, Rau SW (2000) Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury. J Neurocytol 29: 401–410

    Article  PubMed  CAS  Google Scholar 

  • Wise PM, Dubal DB, Wilson ME, Rau SW, Bottner M, Rosewell KL (2001) Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies. Brain Res Rev 37: 313–319

    Article  PubMed  CAS  Google Scholar 

  • Wolf OT, Neumann 0, Hellhammer DH, Geiben AC, Strasburger CJ, Dressendorfer RA, Pirke KM, Kirschbaum C (1997) Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men. J Clin Endocrinol Metab 82: 2363–2367

    Article  PubMed  CAS  Google Scholar 

  • Wolkowitz OM, Reus VI, Roberts E, Manfredi F, Chan T, Ormiston S, Johnson R, Canick J, Brizendine L, Weingartner H (1995) Antidepressant and cognition-enhancing effects of DHEA in major depression. Ann NY Acad Sci 774: 337–339

    Article  PubMed  CAS  Google Scholar 

  • Woodruff RH, Franklin RJM (1999) Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of ethidium bromide, lysolecithin and complement/anti-galactocerebroside–a comparative study. Glia 25: 216–228

    Article  PubMed  CAS  Google Scholar 

  • Yaffe K, Ettinger B, Pressman A, Seeley D, Whooley M, Schaefer C, Cummings S (1998) Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry 43: 694–700

    Article  PubMed  CAS  Google Scholar 

  • Yanase T, Fukahori M, Taniguchi S, Nishi Y, Sakai Y, Takayanagi R, Haji M, Nawata H (1996) Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate ( DHEA-S) in Alzheimer’s disease and in cerebrovascular dementia. Endocrine J 43: 119–123

    Google Scholar 

  • Yu WH (1989) Survival of motoneurons following axotomy is enhanced by lactation or by progesterone treatment. Brain Res 491: 379–382

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Rubinow DR, Xaing G, Li BS, Chang YH, Maric D, Barker JL, Ma W (2001) Estrogen protects against beta-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt. Neuroreport 12: 1919–1923

    Article  PubMed  CAS  Google Scholar 

  • Zwain IH, Yen SS (1999a) Neurosteroidogenesis in astrocytes, oligodendrocytes, and neurons of cerebral cortex of rat brain. Endocrinology 140: 3843–3852

    Article  PubMed  CAS  Google Scholar 

  • Zwain IH, Yen SSC (1999b) Dehydroepiandrosterone (DHEA):biosynthesis and metabolism in the brain. Endocrinology 140: 880–887

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. INSERM U488, Kremlin-Bicêtre, France

    M. Schumacher, C. Ibanez & F. Robert

  2. Instituto Cajal, C.S.I.C., 28002, Madrid, Spain

    L. M. Garcia-Segura

  3. Department of Clinical Veterinary Medicine and Cambridge Center for Brain Repair, University of Cambridge, UK

    R. J. M. Franklin

  4. Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milano, Italy

    R. C. Melcangi

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Schumacher, M., Ibanez, C., Robert, F., Garcia-Segura, L.M., Franklin, R.J.M., Melcangi, R.C. (2004). Aging Myelin and Cognitive Decline: a Role for Steroids. In: Chanson, P., Epelbaum, J., Lamberts, S., Christen, Y. (eds) Endocrine Aspects of Successful Aging: Genes, Hormones and Lifestyles. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-07019-2_7

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  • DOI: https://doi.org/10.1007/978-3-662-07019-2_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-07359-5

  • Online ISBN: 978-3-662-07019-2

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