Protective actions of sex steroid hormones in Alzheimer's disease

Frontiers in Neuroendocrinology

Volumn 30, Issue 2, 2009, Pages 239-258

  Pike, Christian J ^a   Carroll, Jenna C ^a   Rosario, Emily R ^a   Barron, Anna M ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Amyloid; Alzheimer's disease; Estrogen; Neuroprotection; Progesterone; Testosterone

Indexed keywords

AMYLOID BETA PROTEIN; ANDROGEN; ANTIANDROGEN; CONJUGATED ESTROGEN; ESTRADIOL; ESTROGEN; FLUTAMIDE; GESTAGEN; LEUPRORELIN; MEDROXYPROGESTERONE ACETATE; PLACEBO; PROGESTERONE; RALOXIFENE; SELECTIVE ANDROGEN RECEPTOR MODULATOR; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SEX HORMONE; TAMOXIFEN; TESTOSTERONE; TRESTOLONE;

AGING; ALZHEIMER DISEASE; AROMATIZATION; BRAIN INFARCTION; BREAST CANCER; CLINICAL TRIAL; COGNITIVE DEFECT; DEMENTIA; DISEASE PREDISPOSITION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; EXCITOTOXICITY; HIGH RISK POPULATION; HORMONAL REGULATION; HORMONAL THERAPY; HORMONE ACTION; HORMONE RESPONSE; HUMAN; HYPOGONADISM; MENOPAUSAL SYNDROME; MOLECULAR INTERACTION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; POSTMENOPAUSE; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN ASSEMBLY; PROTEIN DEPLETION; REVIEW; RISK BENEFIT ANALYSIS; SEX DIFFERENCE; SIGNAL TRANSDUCTION;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANIMALS; ESTROGEN REPLACEMENT THERAPY; GONADAL STEROID HORMONES; HUMANS; NEUROPROTECTIVE AGENTS; POSTMENOPAUSE;

EID: 67449141652     PISSN: 00913022     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.yfrne.2009.04.015     Document Type: Review

References (390)

1. Aenlle K.K., Kumar A., Cui L., Jackson T.C., and Foster T.C. Estrogen effects on cognition and hippocampal transcription in middle-aged mice. Neurobiol. Aging (2007)
2. Ahlbom E., Prins G.S., and Ceccatelli S. Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism. Brain Res. 892 (2001) 255-262
3. Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G.M., Cooper N.R., Eikelenboom P., Emmerling M., and Fiebich B.L. Inflammation and Alzheimer's disease. Neurobiol. Aging 21 (2000) 383-421
4. Alexander G.M., Swerdloff R.S., Wang C., Davidson T., McDonald V., Steiner B., and Hines M. Androgen-behavior correlations in hypogonadal men and eugonadal men. II. Cognitive abilities. Horm. Behav. 33 (1998) 85-94
5. Alkayed N.J., Murphy S.J., Traystman R.J., Hurn P.D., and Miller V.M. Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke 31 (2000) 161-168
6. Almeida O.P., and Flicker L. Testosterone and dementia: too much ado about too little data. J. Br. Menopause Soc. 9 (2003) 107-110
7. Almeida O.P., Lautenschlager N.T., Vasikaran S., Leedman P., Gelavis A., and Flicker L. A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: effect on mood, cognition and quality of life. Neurobiol. Aging 27 (2006) 141-149
8. Alvarez-De-La-Rosa M., Silva I., Nilsen J., Perez M.M., Garcia-Segura L.M., Avila J., and Naftolin F. Estradiol prevents neural Tau hyperphosphorylation characteristic of Alzheimer's disease. Ann. NY Acad. Sci. 1052 (2005) 210-224
9. Andersen K., Launer L.J., Dewey M.E., Letenneur L., Ott A., Copeland J.R.M., Dartigues J.-F., Kragh-Sorensen P., Baldereschi M., Brayne C., Lobo A., Martinez-Lage J.M., Stijnen T., and Hofman A. Gender differences in the incidence of AD and vascular dementia: the EURODEM studies. Neurology 53 (1999) 1992-1997
10. Anderson R.A., Martin C.W., Kung A.W., Everington D., Pun T.C., Tan K.C., Bancroft J., Sundaram K., Moo-Young A.J., and Baird D.T. 7α-Methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men. J. Clin. Endocrinol. Metab. 84 (1999) 3556-3562
11. Ansonoff M.A., and Etgen A.M. Estradiol elevates protein kinase C catalytic activity in the preoptic area of female rats. Endocrinology 139 (1998) 3050-3056
12. Antonsson B., and Martinou J.C. The Bcl-2 protein family. Exp. Cell. Res. 256 (2000) 50-57
13. Atwood C.S., Meethal S.V., Liu T., Wilson A.C., Gallego M., Smith M.A., and Bowen R.L. Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence. J. Neuropathol. Exp. Neurol. 64 (2005) 93-103
14. Azcoitia I., Sierra A., and Garcia-Segura L.M. Estradiol prevents kainic acid-induced neuronal loss in the rat dentate gyrus. Neuroreport 9 (1998) 3075-3079
15. Azcoitia I., Sierra A., and Garcia_Segura L.M. Neuroprotective effects of estradiol in the adult rat hippocampus: interaction with insulin-like growth factor-I signalling. J. Neurosci. Res. 58 (1999) 815-822
16. Azcoitia I., Sierra A., Veiga S., Honda S., Harada N., and Garcia-Segura L.M. Brain aromatase is neuroprotective. J. Neurobiol. 47 (2001) 318-329
17. Bachman D.L., Wolf P.A., Linn R., Knoefel J.E., Cobb J., Belanger A., D'Agostino R.B., and White L.R. Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham study. Neurology 42 (1992) 115-119
18. Bake S., and Sohrabji F. 17Beta-estradiol differentially regulates blood-brain barrier permeability in young and aging female rats. Endocrinology 145 (2004) 5471-5475
19. Bake S., Ma L., and Sohrabji F. Estrogen receptor-alpha overexpression suppresses 17beta-estradiol-mediated vascular endothelial growth factor expression and activation of survival kinases. Endocrinology 149 (2008) 3881-3889
20. Baker L.D., Sambamurti K., Craft S., Cherrier M., Raskind M.A., Stanczyk F.Z., Plymate S.R., and Asthana S. 17Beta-estradiol reduces plasma Abeta40 for HRT-naive postmenopausal women with Alzheimer disease: a preliminary study. Am J. Geriat. Psychiatry 11 (2003) 239-244
21. Barnes L.L., Wilson R.S., Bienias J.L., Schneider J.A., Evans D.A., and Bennett D.A. Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch. Gen. Psychiatry 62 (2005) 685-691
22. Barret-Connor E., and Kritz-Silverstein D. Estrogen replacement therapy and cognitive function in older women. J. Am. Med. Assoc. 269 (1993) 2637-2641
23. Barrett-Connor E., Goodman-Gruen D., and Patay B. Endogenous sex hormones and cognitive function in older men. J. Clin. Endocrinol. Metab. 84 (1999) 3681-3685
24. Baumgartner R.N., Waters D.L., Gallagher D., Morley J.E., and Garry P.J. Predictors of skeletal muscle mass in elderly men and women. Mech. Ageing Dev. 107 (1999) 123-136
25. Behl C., Davis J.B., Lesley R., and Schubert D. Hydrogen peroxide mediates amyloid b protein toxicity. Cell 77 (1994) 817-827
26. Behl C., Widmann M., Trapp T., and Holsboer F. 17-Beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem. Biophys. Res. Commun. 216 (1995) 473-482
27. Behl C., Trapp T., Skutella T., and Holsboer F. Protection against oxidative stress-induced neuronal cell death - a novel role for RU486. Eur. J. Neurosci. 9 (1997) 912-920
28. Benvenuti S., Luciani P., Vannelli G.B., Gelmini S., Franceschi E., Serio M., and Peri A. Estrogen and selective estrogen receptor modulators exert neuroprotective effects and stimulate the expression of selective Alzheimer's disease indicator-1, a recently discovered antiapoptotic gene, in human neuroblast long-term cell cultures. J. Clin. Endocrinol. Metab. 90 (2005) 1775-1782
29. Bezprozvanny I., and Mattson M.P. Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci. 31 (2008) 454-463
30. Bhasin S., Woodhouse L., Casaburi R., Singh A.B., Bhasin D., Berman N., Chen X., Yarasheski K.E., Magliano L., Dzekov C., Dzekov J., Bross R., Phillips J., Sinha-Hikim I., Shen R., and Storer T.W. Testosterone dose-response relationships in healthy young men. Am. J. Physiol. Endocrinol. Metab. 281 (2001) E1172-1181
31. Bhasin S., Cunningham G.R., Hayes F.J., Matsumoto A.M., Snyder P.J., Swerdloff R.S., and Montori V.M. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 91 (2006) 1995-2010
32. Bimonte-Nelson H.A., Nelson M.E., and Granholm A.C. Progesterone counteracts estrogen-induced increases in neurotrophins in the aged female rat brain. Neuroreport 15 (2004) 2659-2663
33. Bimonte-Nelson H.A., Francis K.R., Umphlet C.D., and Granholm A.C. Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats. Eur. J. Neurosci. 24 (2006) 229-242
34. Binder E.F., Schechtman K.B., Birge S.J., Williams D.B., and Kohrt W.M. Effects of hormone replacement therapy on cognitive performance in elderly women. Maturitas 38 (2001) 137-146
35. Bohacek J., Bearl A.M., and Daniel J.M. Long-term ovarian hormone deprivation alters the ability of subsequent oestradiol replacement to regulate choline acetyltransferase protein levels in the hippocampus and prefrontal cortex of middle-aged rats. J. Neuroendocrinol. 20 (2008) 1023-1027
36. Bohl C.E., Miller D.D., Chen J., Bell C.E., and Dalton J.T. Structural basis for accommodation of nonsteroidal ligands in the androgen receptor. J. Biol. Chem. 280 (2005) 37747-37754
37. Braak H., and Braak E. Alzheimer's disease: striatal amyloid deposits and neurofibrillary changes. J. Neuropathol. Exp. Neurol. 49 (1990) 215-224
38. Brann D.W., Dhandapani K., Wakade C., Mahesh V.B., and Khan M.M. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 72 (2007) 381-405
39. Brayne C., Gill C., Huppert F.A., Barkley C., Gehlhaar E., Girling D.M., O'Connor D.W., and Paykel E.S. Incidence of clinically diagnosed subtypes of dementia in an elderly population. Cambridge Project for Later Life. Br. J. Psychiatry 167 (1995) 255-262
40. Brenner D.E., Kukull W.A., Stergachis A., van Belle G., Bowen J.D., McCormick W.C., Teri L., and Larson E.B. Postmenopausal estrogen replacement therapy and the risk of Alzheimer's disease: a population-based case-control study. Am. J. Epidemiol. 140 (1994) 262-267
41. Breuer B., and Anderson R. The relationship of tamoxifen with dementia, depression, and dependence in activities of daily living in elderly nursing home residents. Women Health 31 (2000) 71-85
42. Brinton R.D. Requirements of a brain selective estrogen: advances and remaining challenges for developing a NeuroSERM. J. Alzheimers Dis. 6 (2004) S27-35
43. Brinton R.D., Chen S., Montoya M., Hsieh D., and Minaya J. The estrogen replacement therapy of the Women's Health Initiative promotes the cellular mechanisms of memory and neuronal survival in neurons vulnerable to Alzheimer's disease. Maturitas 34 Suppl. 2 (2000) S35-52
44. Brinton R.D., Thompson R.F., Foy M.R., Baudry M., Wang J., Finch C.E., Morgan T.E., Pike C.J., Mack W.J., Stanczyk F.Z., and Nilsen J. Progesterone receptors: form and function in brain. Front. Neuroendocrinol. 29 (2008) 313-339
45. Brooks B.P., Merry D.E., Paulson H.L., Lieberman A.P., Kolson D.L., and Fischbeck K.H. A cell culture model for androgen effects in motor neurons. J. Neurochem. 70 (1998) 1054-1060
46. Brown T.R. Nonsteroidal selective androgen receptors modulators (SARMs): designer androgens with flexible structures provide clinical promise. Endocrinology 145 (2004) 5417-5419
47. Bruce-Keller A.J., Keeling J.L., Keller J.N., Huang F.F., Camondola S., and Mattson M.P. Antiinflammatory effects of estrogen on microglial activation. Endocrinology 141 (2000) 3646-3656
48. Bryant H.U., and Dere W.H. Selective estrogen receptor modulators: an alternative to hormone replacement therapy. Proc. Soc. Exp. Biol. Med. 217 (1998) 45-52
49. Buckwalter J.G., Sobel E., Dunn M.E., Diz M.M., and Henderson V.W. Gender differences on a brief measure of cognitive functioning in Alzheimer's disease. Arch. Neurol. 50 (1993) 757-760
50. Burger H., de Laet C.E., van Daele P.L., Weel A.E., Witteman J.C., Hofman A., and Pols H.A. Risk factors for increased bone loss in an elderly population: the Rotterdam study. Am. J. Epidemiol. 147 (1998) 871-879
51. Callahan M.J., Lipinski W.J., Bian F., Durham R.A., Pack A., and Walker L.C. Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic mice. Am. J. Pathol. 158 (2001) 1173-1177
52. Carlson M.C., Zandi P.P., Plassman B.L., Tschanz J.T., Welsh-Bohmer K.A., Steffens D.C., Bastian L.A., Mehta K.M., and Breitner J.C. Hormone replacement therapy and reduced cognitive decline in older women: the Cache County Study. Neurology 57 (2001) 2210-2216
53. Carroll J.C., and Pike C.J. Selective estrogen receptor modulators differentially regulate Alzheimer-like changes in female 3xTg-AD mice. Endocrinology 149 (2008) 2607-2611
54. Carroll J.C., Rosario E.R., Chang L., Stanczyk F.Z., Oddo S., LaFerla F.M., and Pike C.J. Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J. Neurosci. 27 (2007) 13357-13365
55. Carroll J.C., Rosario E.R., and Pike C.J. Progesterone blocks estrogen neuroprotection from kainate in middle-aged female rats. Neurosci. Lett. 445 (2008) 229-232
56. Castelo-Branco C., Figueras F., Sanjuan A., Pons F., Vicente J.J., and Vanrell J.A. Long-term postmenopausal hormone replacement therapy effects on bone mass: differences between surgical and spontaneous patients. Eur. J. Obstet. Gynecol. Reprod. Biol. 83 (1999) 207-211
57. Chae H.S., Bach J.H., Lee M.W., Kim H.S., Kim Y.S., Kim K.Y., Choo K.Y., Choi S.H., Park C.H., Lee S.H., Suh Y.H., Kim S.S., and Lee W.B. Estrogen attenuates cell death induced by carboxy-terminal fragment of amyloid precursor protein in PC12 through a receptor-dependent pathway. J. Neurosci. Res. 65 (2001) 403-407
58. Chakraborty T.R., and Gore A.C. Aging-related changes in ovarian hormones, their receptors, and neuroendocrine function. Exp. Biol. Med. (Maywood) 229 (2004) 977-987
59. Chang D., Kwan J., and Timiras P.S. Estrogens influence growth, maturation, and amyloid beta-peptide production in neuroblastoma cells and in a beta-APP transfected kidney 293 cell line. Adv. Exp. Med. Biol. 429 (1997) 261-271
60. Chaovipoch P., Jelks K.A., Gerhold L.M., West E.J., Chongthammakun S., and Floyd C.L. 17Beta-estradiol is protective in spinal cord injury in post- and pre-menopausal rats. J. Neurotrauma. 23 (2006) 830-852
61. Cheng I.H., Scearce-Levie K., Legleiter J., Palop J.J., Gerstein H., Bien-Ly N., Puolivali J., Lesne S., Ashe K.H., Muchowski P.J., and Mucke L. Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J. Biol. Chem. 282 (2007) 23818-23828
62. Cherrier M.M., Asthana S., Plymate S., Baker L., Matsumoto A.M., Peskind E., Raskind M.A., Brodkin K., Bremner W., Petrova A., LaTendresse S., and Craft S. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology 57 (2001) 80-88
63. Cherrier M.M., Matsumoto A.M., Amory J.K., Asthana S., Bremner W., Peskind E.R., Raskind M.A., and Craft S. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology 64 (2005) 2063-2068
64. Choi D.W. Ionic dependence of glutamate neurotoxicity. J. Neurosci. 7 (1987) 369-379
65. Ciana P., Di Luccio G., Belcredito S., Pollio G., Vegeto E., Tatangelo L., Tiveron C., and Maggi A. Engineering of a mouse for the in vivo profiling of estrogen receptor activity. Mol. Endocrinol. 15 (2001) 1104-1113
66. Corder E.H., Ghebremedhin E., Taylor M.G., Thal D.R., Ohm T.G., and Braak H. The biphasic relationship between regional brain senile plaque and neurofibrillary tangle distributions: modification by age, sex, and APOE polymorphism. Ann. NY Acad. Sci. 1019 (2004) 24-28
67. Cordey M., and Pike C.J. Neuroprotective properties of selective estrogen receptor agonists in cultured neurons. Brain Res. 1045 (2005) 217-223
68. Cordey M., and Pike C.J. Conventional protein kinase C isoforms mediate neuroprotection induced by phorbol ester and estrogen. J. Neurochem. 96 (2006) 204-217
69. Cordey M., Gundimeda U., Gopalakrishna R., and Pike C.J. Estrogen activates protein kinase C in neurons: role in neuroprotection. J. Neurochem. 84 (2003) 1340-1348
70. Cory S., and Adams J.M. The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2 (2002) 647-656
71. Cotman C.W., and Anderson A.J. A potential role for apoptosis in neurodegeneration and Alzheimer's disease. Mol. Neurobiol. 10 (1995) 19-45
72. Cotman C.W., Pike C.J., and Copani A. Beta-Amyloid neurotoxicity: a discussion of in vitro findings. Neurobiol. Aging 13 (1992) 587-590
73. C.W. Cotman, D.H. Cribbs, C.J. Pike, K.J. Ivins, Cell death in Alzheimer's death. When Cells Die: A Comprehensive Evaluation of Apoptosis and Programmed Cell Death, 1998, pp. 385-409.
74. Coughlan C.M., and Breen K.C. Factors influencing the processing and function of the amyloid beta precursor protein - a potential therapeutic target in Alzheimer's disease?. Pharmacol. Ther. 86 (2000) 111-144
75. Craig M.C., Maki P.M., and Murphy D.G. The Women's Health Initiative memory study: findings and implications for treatment. Lancet Neurol. 4 (2005) 190-194
76. Cummings D.E., Kumar N., Bardin C.W., Sundaram K., and Bremner W.J. Prostate-sparing effects in primates of the potent androgen 7alpha-methyl-19-nortestosterone: a potential alternative to testosterone for androgen replacement and male contraception. J. Clin. Endocrinol. Metab. 83 (1998) 4212-4219
77. Dai D., Wolf D.M., Litman E.S., White M.J., and Leslie K.K. Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res. 62 (2002) 881-886
78. Daniel J.M., Hulst J.L., and Berbling J.L. Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation. Endocrinology 147 (2006) 607-614
79. Davies S., Dai D., Wolf D.M., and Leslie K.K. Immunomodulatory and transcriptional effects of progesterone through progesterone A and B receptors in Hec50co poorly differentiated endometrial cancer cells. J. Soc. Gynecol. Investig. 11 (2004) 494-499
80. Del Cerro S., Garcia-Estrada J., and Garcia-Segura L.M. Neuroactive steroids regulate astroglia morphology in hippocampal cultures from adult rats. Glia 14 (1995) 65-71
81. Delmas P.D., Bjarnason N.H., Mitlak B.H., Ravoux A.C., Shah A.S., Huster W.J., Draper M., and Christiansen C. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. New Engl. J. Med. 337 (1997) 1641-1647
82. Dluzen D.E. Effects of testosterone upon MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system of C57/B1 mice. Brain Res. 715 (1996) 113-118
83. Dong L., Wang W., Wang F., Stoner M., Reed J.C., Harigai M., Samudio I., Kladde M.P., Vyhlidal C., and Safe S. Mechanisms of transcriptional activation of Bcl-2 gene expression by 17beta-estradiol in breast cancer cells. J. Biol. Chem. 274 (1999) 32099-32107
84. Duara R., Barker W.W., Lopez-Alberola R., Loewenstein D.A., Grau L.B., Gilchrist D., Sevush S., and St George-Hyslop S. Alzheimer's disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset. Neurology 46 (1996) 1575-1579
85. Dubal D.B., and Wise P.M. Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology 142 (2001) 43-48
86. Dubal D.B., Shughrue P.J., Wilson M.E., Merchenthaler I., and Wise P.M. Estradiol modulates Bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J. Neurosci. 19 (1999) 6385-6393
87. Edinger K.L., and Frye C.A. Testosterone's analgesic, anxiolytic, and cognitive-enhancing effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus. Behav. Neurosci. 118 (2004) 1352-1364
88. Edinger K.L., and Frye C.A. Testosterone's anti-anxiety and analgesic effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus. Psychoneuroendocrinology 30 (2005) 418-430
89. El Khoury J., Hickman S.E., Thomas C.A., Cao L., Silverstein S.C., and Loike J.D. Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature 382 (1996) 716-719
90. Emmelot-Vonk M.H., Verhaar H.J., Nakhai Pour H.R., Aleman A., Lock T.M., Bosch J.L., Grobbee D.E., and van der Schouw Y.T. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. Jama 299 (2008) 39-52
91. Espeland M.A., Rapp S.R., Shumaker S.A., Brunner R., Manson J.E., Sherwin B.B., Hsia J., Margolis K.L., Hogan P.E., Wallace R., Dailey M., Freeman R., and Hays J. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. Jama 291 (2004) 2959-2968
92. 2+ oscillations induced by testosterone enhance neurite outgrowth. J. Cell Sci. 119 (2006) 733-743
93. Farrer L.A., Cupples L.A., Haines J.L., Hyman B., Kukull W.A., Mayeux R., Myers R.H., Pericak-Vance M.A., Risch N., and van Duijn C.M. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. Jama 278 (1997) 1349-1356
94. Feldman H.A., Longcope C., Derby C.A., Johannes C.B., Araujo A.B., Coviello A.D., Bremner W.J., and McKinlay J.B. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J. Clin. Endocrinol. Metab. 87 (2002) 589-598
95. Felicio L.S., Nelson J.F., and Finch C.E. Longitudinal studies of estrous cyclicity in aging C57BL/6J mice: II. Cessation of cyclicity and the duration of persistent vaginal cornification. Biol. Reprod. 31 (1984) 446-453
96. Ferrando A.A., Sheffield-Moore M., Yeckel C.W., Gilkison C., Jiang J., Achacosa A., Lieberman S.A., Tipton K., Wolfe R.R., and Urban R.J. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am. J. Physiol. Endocrinol. Metab. 282 (2002) E601-607
97. Fitzpatrick J.L., Mize A.L., Wade C.B., Harris J.A., Shapiro R.A., and Dorsa D.M. Estrogen-mediated neuroprotection against beta-amyloid toxicity requires expression of estrogen receptor alpha or beta and activation of the MAPK pathway. J. Neurochem. 82 (2002) 674-682
98. Fleisher A., Grundman M., Jack Jr. C.R., Petersen R.C., Taylor C., Kim H.T., Schiller D.H., Bagwell V., Sencakova D., Weiner M.F., DeCarli C., DeKosky S.T., van Dyck C.H., and Thal L.J. Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment. Arch. Neurol. 62 (2005) 953-957
99. Fleshner N., and Zlotta A.R. Prostate cancer prevention: past, present, and future. Cancer 110 (2007) 1889-1899
100. Frankfurt M., Gould E., Woolley C.S., and McEwen B.S. Gonadal steroids modify dendritic spine density in ventromedial hypothalamic neurons: a Golgi study in the adult rat. Neuroendocrinology 51 (1990) 530-535
101. Fratiglioni L., Viitanen M., von Strauss E., Tontodonati V., Herlitz A., and Winblad B. Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm. Neurology 48 (1997) 132-138
102. Frye C.A., and Reed T.A. Androgenic neurosteroids: anti-seizure effects in an animal model of epilepsy. Psychoneuroendocrinology 23 (1998) 385-399
103. Frye C.A., and Seliga A.M. Testosterone increases analgesia, anxiolysis, and cognitive performance of male rats. Cogn. Affect. Behav. Neurosci. 1 (2001) 371-381
104. Frye C.A., and Walf A.A. Effects of progesterone administration and APPswe+PSEN1Deltae9 mutation for cognitive performance of mid-aged mice. Neurobiol. Learn. Mem. 89 (2008) 17-26
105. Fukuzaki E., Takuma K., Funatsu Y., Himeno Y., Kitahara Y., Gu B., Mizoguchi H., Ibi D., Koike K., Inoue M., Yan S.D., and Yamada K. Ovariectomy increases neuronal amyloid-beta binding alcohol dehydrogenase level in the mouse hippocampus. Neurochem. Int. 52 (2008) 1358-1364
106. Gandy S., and Petanceska S. Regulation of alzheimer beta-amyloid precursor trafficking and metabolism. Adv. Exp. Med. Biol. 487 (2001) 85-100
107. Gandy S., Almeida O.P., Fonte J., Lim D., Waterrus A., Spry N., Flicker L., and Martins R.N. Chemical andropause and amyloid-beta peptide. J. Am. Med. Assoc. 285 (2001) 2195-2196
108. Gao W., Reiser P.J., Coss C.C., Phelps M.A., Kearbey J.D., Miller D.D., and Dalton J.T. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology 146 (2005) 4887-4897
109. Garcia-Estrada J., Del Rio J.A., Luquin S., Soriano E., and Garcia-Segura L.M. Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury. Brain Res. 628 (1993) 271-278
110. Garcia-Segura L.M., Cardona-Gomez P., Naftolin F., and Chowen J.A. Estradiol upregulates Bcl-2 expression in adult brain neurons. Neuroreport 9 (1998) 593-597
111. Garcia-Segura L.M., Wozniak A., Azcoitia I., Rodriguez J.R., Hutchison R.E., and Hutchison J.B. Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience 89 (1999) 567-578
112. Gatson J.W., and Singh M. Activation of a membrane-associated androgen receptor promotes cell death in primary cortical astrocytes. Endocrinology 148 (2007) 2458-2464
113. Gatson J.W., Kaur P., and Singh M. Dihydrotestosterone differentially modulates the mitogen-activated protein kinase and the phosphoinositide 3-kinase/Akt pathways through the nuclear and novel membrane androgen receptor in C6 cells. Endocrinology 147 (2006) 2028-2034
114. Gee D.M., Flurkey K., and Finch C.E. Aging and the regulation of luteinizing hormone in C57BL/6J mice: impaired elevations after ovariectomy and spontaneous elevations at advanced ages. Biol. Reprod. 28 (1983) 598-607
115. Gibbs R.B. Effects of gonadal hormone replacement on measures of basal forebrain cholinergic function. Neuroscience 101 (2000) 931-938
116. R.B. Gibbs, Oestrogen and the cholinergic hypothesis: implications for oestrogen replacement therapy in postmenopausal women, Novartis Found Symp 230 (2000) 94-107; discussion 107-111.
117. Gillett M.J., Martins R.N., Clarnette R.M., Chubb S.A., Bruce D.G., and Yeap B.B. Relationship between testosterone, sex hormone binding globulin and plasma amyloid beta peptide 40 in older men with subjective memory loss or dementia. J. Alzheimers Dis. 5 (2003) 267-269
118. Gleason C.E., Carlsson C.M., Johnson S., Atwood C., and Asthana S. Clinical pharmacology and differential cognitive efficacy of estrogen preparations. Ann. NY Acad. Sci. 1052 (2005) 93-115
119. Goebel J.A., Birge S.J., Price S.C., Hanson J.M., and Fishel D.G. Estrogen replacement therapy and postural stability in the elderly. Am. J. Otolaryng. 16 (1995) 470-474
120. Golub M.S., Germann S.L., Mercer M., Gordon M.N., Morgan D.G., Mayer L.P., and Hoyer P.B. Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe mouse. Neurobiol. Aging 29 (2007) 1512-1523
121. Goodenough S., Engert S., and Behl C. Testosterone stimulates rapid secretory amyloid precursor protein release from rat hypothalamic cells via the activation of the mitogen-activated protein kinase pathway. Neurosci. Lett. 296 (2000) 49-52
122. Goodenough S., Schleusner D., Pietrzik C., Skutella T., and Behl C. Glycogen synthase kinase 3beta links neuroprotection by 17beta-estradiol to key Alzheimer processes. Neuroscience 132 (2005) 581-589
123. Goodman Y., and Mattson M.P. Secreted forms of b-amyloid precursor protein protect hippocampal neurons against amyloid b-peptide-induced oxidative injury. Exp. Neurol. 128 (1994) 1-12
124. Goodman Y., Bruce A.J., Cheng B., and Mattson M.P. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J. Neurochem. 66 (1996) 1836-1844
125. Gooren L. Androgen deficiency in the aging male: benefits and risks of androgen supplementation. J. Steroid. Biochem. Mol. Biol. 85 (2003) 349-355
126. Gosden R.G., Laing S.C., Felicio L.S., Nelson J.F., and Finch C.E. Imminent oocyte exhaustion and reduced follicular recruitment mark the transition to acyclicity in aging C57BL/6J mice. Biol. Reprod. 28 (1983) 255-260
127. Gouchie C., and Kimura D. The relationship between testosterone levels and cognitive ability patterns. Psychoneuroendocrinology 16 (1991) 323-334
128. Gouras G.K., Xu H., Gross R.S., Greenfield J.P., Hai B., Wang R., and Greengard P. Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. PNAS 97 (2000) 1202-1205
129. Grady D., Gebretsadik T., Kerlikowske K., Ernster V., and Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet. Gynecol. 85 (1995) 304-313
130. Graham J.D., and Clarke C.L. Physiological action of progesterone in target tissues. Endocr. Rev. 18 (1997) 502-519
131. Gray A., Feldman H., McKinlay J., and Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts male aging study. J. Clin. Endocrinol. Metab. 73 (1991) 1016-1025
132. Green P.S., Gridley K.E., and Simpkins J.W. Estradiol protects against beta-amyloid (25-35)-induced toxicity in SK-N-SH human neuroblastoma cells. Neurosci. Lett. 218 (1996) 165-168
133. Green P.S., Bales K., Paul S., and Bu G.J. Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease. Endocrinology 146 (2005) 2774-2781
134. Greenfield J.P., Leung L.W., Cai D., Kaasik K., Gross R.S., Rodriguez_Boulan E., Greengard P., and Xu H. Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi network vesicle biogenesis. J. Biol. Chem. 277 (2002) 12128-12136
135. Gridley K.E., Green P.S., and Simpkins J.W. Low concentrations of estradiol reduce b-amyloid (25-35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells. Brain Res. 778 (1997) 158-165
136. Haass C., and Selkoe D.J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 8 (2007) 101-112
137. Hagnell O., Ojesjo L., and Rorsman B. Incidence of dementia in the Lundby study. Neuroepidemiology 11 Suppl. 1 (1992) 61-66
138. Hammond J., Le Q., Goodyer C., Gelfand M., Trifiro M., and LeBlanc A. Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons. J. Neurochem. 77 (2001) 1319-1326
139. Hardy J. The Alzheimer family of diseases: many etiologies, one pathogenesis?. Proc. Natl. Acad. Sci. USA 94 (1997) 2095-2097
140. Hardy J.A., and Higgins G.A. Alzheimer's disease: the amyloid cascade hypothesis. Science 256 (1992) 184-185
141. Haren M.T., Wittert G.A., Chapman I.M., Coates P., and Morley J.E. Effect of oral testosterone undecanoate on visuospatial cognition, mood and quality of life in elderly men with low-normal gonadal status. Maturitas 50 (2005) 124-133
142. Haren M.T., Kim M.J., Tariq S.H., Wittert G.A., and Morley J.E. Andropause: a quality-of-life issue in older males. Med. Clin. North Am. 90 (2006) 1005-1023
143. Harris-White M.E., Chu T., Miller S.A., Simmons M., Teter B., Nash D., Cole G.M., and Frautschy S.A. Estrogen (E2) and glucocorticoid (Gc) effects on microglia and Ab clearance in vitro and in vivo. Neurochem. Int. 39 (2001) 435-448
144. Hart S.A., Patton J.D., and Woolley C.S. Quantitative analysis of ERalpha and GAD colocalization in the hippocampus of the adult female rat. J. Comp. Neurol. 440 (2001) 144-155
145. Hartley D.M., Walsh D.M., Ye C.P., Diehl T., Vasquez S., Vassilev P.M., Teplow D.B., and Selkoe D.J. Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J. Neurosci. 19 (1999) 8876-8884
146. Haskell S.G., Richardson E.D., and Horwitz R.I. The effect of estrogen replacement therapy on cognitive function in women: a critical review of the literature. J. Clin. Epidemiol. 50 (1997) 1249-1264
147. He B., Minges J.T., Lee L.W., and Wilson E.M. The FXXLF motif mediates androgen receptor-specific interactions with coregulators. J. Biol. Chem. 277 (2002) 10226-10235
148. Heikkinen T., Kalesnykas G., Rissanen A., Tapiola T., Iivonen S., Wang J., Chaudhuri J., Tanila H., Miettinen R., and Puolivali J. Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation. Exp. Neurol. 187 (2004) 105-117
149. Henderson V.W. Estrogen-containing hormone therapy and Alzheimer's disease risk: understanding discrepant inferences from observational and experimental research. Neuroscience 138 (2006) 1031-1039
150. Henderson V., and Buckwalter J. Cognitive deficits of men and women with Alzheimer's disease. Neurology 44 (1994) 90-96
151. Henderson V.W., Paganini-Hill A., Emanuel C.K., Dunn M.E., and Buckwalter J.G. Estrogen replacement therapy in older women. Comparisons between Alzheimer's disease cases and nondemented control subjects. Arch. Neurol. 51 (1994) 896-900
152. Henderson V.W., Paganini_Hill A., Miller B.L., Elble R.J., Reyes P.F., Shoupe D., McCleary C.A., Klein R.A., Hake A.M., and Farlow M.R. Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial. Neurology 54 (2000) 295-301
153. Henderson V.W., Guthrie J.R., Dudley E.C., Burger H.G., and Dennerstein L. Estrogen exposures and memory at midlife: a population-based study of women. Neurology 60 (2003) 1369-1371
154. Henderson V.W., Benke K.S., Green R.C., Cupples L.A., and Farrer L.A. Postmenopausal hormone therapy and Alzheimer's disease risk: interaction with age. J. Neurol. Neurosurg. Psychiatry 76 (2005) 103-105
155. Hestiantoro A., and Swaab D.F. Changes in estrogen receptor-alpha and -beta in the infundibular nucleus of the human hypothalamus are related to the occurrence of Alzheimer's disease neuropathology. J. Clin. Endocrinol. Metab. 89 (2004) 1912-1925
156. Hirata-Fukae C., Li H.F., Hoe H.S., Gray A.J., Minami S.S., Hamada K., Niikura T., Hua F., Tsukagoshi-Nagai H., Horikoshi-Sakuraba Y., Mughal M., Rebeck G.W., LaFerla F.M., Mattson M.P., Iwata N., Saido T.C., Klein W.L., Duff K.E., Aisen P.S., and Matsuoka Y. Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res. 1216 (2008) 92-103
157. Hlatky M.A., Boothroyd D., Vittinghoff E., Sharp P., and Whooley M.A. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. Jama 287 (2002) 591-597
158. Hogervorst E., Boshuisen M., Riedel W., Willeken C., and Jolles J. 1998 Curt P. Richter Award. The effect of hormone replacement therapy on cognitive function in elderly women. Psychoneuroendocrinology 24 (1999) 43-68
159. Hogervorst E., Williams J., Biudge M., Barnetson L., Combrinck M., and Smith A.D. Serum total testosterone is lower in men with Alzheimer's disease. Neuroendocrinol. Lett. 22 (2001) 163-168
160. Hogervorst E., Lehmann D.J., Warden D.R., McBroom J., and Smith A.D. Apolipoprotein E epsilon4 and testosterone interact in the risk of Alzheimer's disease in men. Int. J. Geriatr. Psych. 17 (2002) 938-940
161. Hogervorst E., Combrinck M., and Smith A.D. Testosterone and gonadotropin levels in men with dementia. Neuroendocrinol. Lett. 24 (2003) 203-208
162. Honjo H., Iwasa K., Kawata M., Fushiki S., Hosoda T., Tatsumi H., Oida N., Mihara M., Hirasugi Y., Yamamoto H., Kikuchi N., and Kitawaki J. Progestins and estrogens and Alzheimer's disease. J. Steroid. Biochem. Mol. Biol. 93 (2005) 305-308
163. Huang J., Guan H., Booze R.M., Eckman C.B., and Hersh L.B. Estrogen regulates neprilysin activity in rat brain. Neurosci. Lett. 367 (2004) 85-87
164. Huppenbauer C.B., Tanzer L., DonCarlos L.L., and Jones K.J. Gonadal steroid attenuation of developing hamster facial motoneuron loss by axotomy: equal efficacy of testosterone, dihydrotestosterone, and 17-beta estradiol. J. Neurosci. 25 (2005) 4004-4013
165. Hyman B.T., Gomez-Isla T., Briggs M., Chung H., Nichols S., Kohout F., and Wallace R. Apolipoprotein E and cognitive change in an elderly population. Ann. Neurol. 40 (1996) 55-66
166. Iqbal K., Alonso Adel C., Chen S., Chohan M.O., El-Akkad E., Gong C.X., Khatoon S., Li B., Liu F., Rahman A., Tanimukai H., and Grundke-Iqbal I. Tau pathology in Alzheimer disease and other tauopathies. Biochim. Biophys. Acta 1739 (2005) 198-210
167. Irwin R.W., Yao J., Hamilton R.T., Cadenas E., Brinton R.D., and Nilsen J. Progesterone and estrogen regulate oxidative metabolism in brain mitochondria. Endocrinology 149 (2008) 3167-3175
168. Islander U., Erlandsson M.C., Hasseus B., Jonsson C.A., Ohlsson C., Gustafsson J.A., Dahlgren U., and Carlsten H. Influence of oestrogen receptor alpha and beta on the immune system in aged female mice. Immunology 110 (2003) 149-157
169. Ivins K.J., Bui E.T., and Cotman C.W. Beta-amyloid induces local neurite degeneration in cultured hippocampal neurons: evidence for neuritic apoptosis. Neurobiol. Dis. 5 (1998) 365-378
170. Iwata N., Tsubuki S., Takaki Y., Watanabe K., Sekiguchi M., Hosoki E., Kawashima-Morishima M., Lee H.J., Hama E., Sekine-Aizawa Y., and Saido T.C. Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat. Med. 6 (2000) 143-150
171. Jaffe A.B., Toran_Allerand C.D., Greengard P., and Gandy S.E. Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. J. Biol. Chem. 269 (1994) 13065-13068
172. Janowsky J.S., Oviatt S.K., and Orwoll E.S. Testosterone influences spatial cognition in older men. Behav. Neurosci. 108 (1994) 325-332
173. Janowsky J.S., Chavez B., and Orwoll E. Sex steroids modify working memory. J. Cogn. Neurosci. 12 (2000) 407-414
174. Jayaraman A., and Pike C.J. Progesterone attenuates oestrogen neuroprotection via downregulation of oestrogen receptor expression in cultured neurones. J. Neuroendocrinol. 21 (2009) 77-81
175. Jezierski M.K., and Sohrabji F. Neurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation. Neurobiol. Aging 22 (2001) 309-319
176. Johnson A.B., Bake S., Lewis D.K., and Sohrabji F. Temporal expression of IL-1beta protein and mRNA in the brain after systemic LPS injection is affected by age and estrogen. J. Neuroimmunol. 174 (2006) 82-91
177. Jones K.J., Coers S., Storer P.D., Tanzer L., and Kinderman N.B. Androgenic regulation of the central glia response following nerve damage. J. Neurobiol. 40 (1999) 560-573
178. Jones K.J., Brown T.J., and Damaser M. Neuroprotective effects of gonadal steroids on regenerating peripheral motoneurons. Brain Res. Brain Res. Rev. 37 (2001) 372-382
179. Jones R.D., Pugh P.J., Hall J., Channer K.S., and Jones T.H. Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse. Eur. J. Endocrinol./Eur. Fed. Endocr. Soc. 148 (2003) 111-120
180. Jorm A.F., Korten A.E., and Henderson A.S. The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr. Scand. 76 (1987) 465-479
181. Kalesnykas G., Roschier U., Puolivali J., Wang J., and Miettinen R. The effect of aging on the subcellular distribution of estrogen receptor-alpha in the cholinergic neurons of transgenic and wild-type mice. Eur. J. Neurosci. 21 (2005) 1437-1442
182. Kamenetz F., Tomita T., Hsieh H., Seabrook G., Borchelt D., Iwatsubo T., Sisodia S., and Malinow R. APP processing and synaptic function. Neuron 37 (2003) 925-937
183. Kaufman J.M., and Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr. Rev. (2005)
184. Kawas C., Resnick S., Morrison A., Brookmeyer R., Corrada M., Zonderman A., Bacal C., Donnell Lingle D., and Metter E. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore longitudinal study of aging. Neurology 48 (1997) 1517-1521
185. Kelly J.F., Bienias J.L., Shah A., Meeke K.A., Schneider J.A., Soriano E., and Bennett D.A. Levels of estrogen receptors alpha and beta in frontal cortex of patients with Alzheimer's disease: relationship to Mini-Mental State Examination scores. Curr. Alzheimer Res. 5 (2008) 45-51
186. Kilbourne E.J., Moore W.J., Freedman L.P., and Nagpal S. Selective androgen receptor modulators for frailty and osteoporosis. Curr. Opin. Investig. Drugs 8 (2007) 821-829
187. Kim H., Bang O.Y., Jung M.W., Ha S.D., Hong H.S., Huh K., Kim S.U., and Mook-Jung I. Neuroprotective effects of estrogen against beta-amyloid toxicity are mediated by estrogen receptors in cultured neuronal cells. Neurosci. Lett. 302 (2001) 58-62
188. Kim J., Wu D., Hwang D.J., Miller D.D., and Dalton J.T. The para substituent of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-pr op ionamides is a major structural determinant of in vivo disposition and activity of selective androgen receptor modulators. J. Pharmacol. Exp. Ther. 315 (2005) 230-239
189. Koh J.Y., Yang L.L., and Cotman C.W. Beta-amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage. Brain Res. 533 (1990) 315-320
190. Koo E. Phorbol esters affect multiple steps in beta-amyloid precursor protein trafficking and amyloid beta-protein production. Mol. Med. 3 (1997) 204-211
191. Koski C.L., Hila S., and Hoffman G.E. Regulation of cytokine-induced neuron death by ovarian hormones: involvement of antiapoptotic protein expression and c-JUN N-terminal kinase-mediated proapoptotic signaling. Endocrinology 145 (2004) 95-103
192. Kujawa K.A., Kinderman N.B., and Jones K.J. Testosterone-induced acceleration of recovery from facial paralysis following crush axotomy of the facial nerve in male hamsters. Exp. Neurol. 105 (1989) 80-85
193. Kujawa K.A., Emeric E., and Jones K.J. Testosterone differentially regulates the regenerative properties of injured hamster facial motoneurons. J. Neurosci. 11 (1991) 3898-3906
194. Kujawa K.A., Jacob J.M., and Jones K.J. Testosterone regulation of the regenerative properties of injured rat sciatic motor neurons. J. Neurosci. Res. 35 (1993) 268-273
195. Kujawa K.A., Tanzer L., and Jones K.J. Inhibition of the accelerative effects of testosterone on hamster facial nerve regeneration by the antiandrogen flutamide. Exp. Neurol. 133 (1995) 138-143
196. LaFerla F.M., and Oddo S. Alzheimer's disease: Abeta, tau and synaptic dysfunction. Trends Mol. Med. 11 (2005) 170-176
197. LeBlanc E.S., Janowsky J., Chan B.K.S., and Nelson H.D. Hormone replacement therapy and cognition: systematic review and meta-analysis. J. Am. Med. Assoc. 285 (2001) 1489
198. Lesne S., Koh M.T., Kotilinek L., Kayed R., Glabe C.G., Yang A., Gallagher M., and Ashe K.H. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440 (2006) 352-357
199. Levin-Allerhand J.A., Lominska C.E., Wang J., and Smith J.D. 17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in AbetaPPSWE transgenic mice. J. Alzheimers Dis. 4 (2002) 449-457
200. Li R., Shen Y., Yang L.B., Lue L.F., Finch C., and Rogers J. Estrogen enhances uptake of amyloid beta-protein by microglia derived from the human cortex. J. Neurochem. 75 (2000) 1447-1454
201. Li J.J., Sutton J.C., Nirschl A., Zou Y., Wang H., Sun C., Pi Z., Johnson R., Krystek Jr. S.R., Seethala R., Golla R., Sleph P.G., Beehler B.C., Grover G.J., Fura A., Vyas V.P., Li C.Y., Gougoutas J.Z., Galella M.A., Zahler R., Ostrowski J., and Hamann L.G. Discovery of potent and muscle selective androgen receptor modulators through Scaffold modifications. J. Med. Chem. 50 (2007) 3015-3025
202. Liehr J.G., and Roy D. Free radical generation by redox cycling of estrogens. Free Rad. Biol. Med. 8 (1990) 415-423
203. Linford N., Wade C., and Dorsa D. The rapid effects of estrogen are implicated in estrogen-mediated neuroprotection. J. Neurocytol. 29 (2000) 367-374
204. Liu X.A., Zhu L.Q., Zhang Q., Shi H.R., Wang S.H., Wang Q., and Wang J.Z. Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase-A. Neurochem. Res. 33 (2008) 1811-1820
205. Lu Y.P., Zeng M., Swaab D.F., Ravid R., and Zhou J.N. Colocalization and alteration of estrogen receptor-alpha and -beta in the hippocampus in Alzheimer's disease. Hum. Pathol. 35 (2004) 275-280
206. Lu P.H., Masterman D.A., Mulnard R., Cotman C., Miller B., Yaffe K., Reback E., Porter V., Swerdloff R., and Cummings J.L. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch. Neurol. 63 (2006) 177-185
207. MacLusky N.J., Hajszan T., and Leranth C. Effects of dehydroepiandrosterone and flutamide on hippocampal CA1 spine synapse density in male and female rats: implications for the role of androgens in maintenance of hippocampal structure. Endocrinology 145 (2004) 4154-4161
208. MacLusky N.J., Hajszan T., Prange-Kiel J., and Leranth C. Androgen modulation of hippocampal synaptic plasticity. Neuroscience 138 (2006) 957-965
209. Maki P. Hormone therapy and risk for dementia: where do we go from here?. Gynecol. Endocrinol. 19 (2003) 354
210. Maki P.M., Ernst M., London E.D., Mordecai K.L., Perschler P., Durso S.C., Brandt J., Dobs A., and Resnick S.M. Intramuscular testosterone treatment in elderly men: evidence of memory decline and altered brain function. J. Clin. Endocrinol. Metab. 92 (2007) 4107-4114
211. Manfredi M.C., Bi Y., Nirschl A.A., Sutton J.C., Seethala R., Golla R., Beehler B.C., Sleph P.G., Grover G.J., Ostrowski J., and Hamann L.G. Synthesis and SAR of tetrahydropyrrolo[1,2-b][1,2,5]thiadiazol-2(3H)-one 1,1-dioxide analogues as highly potent selective androgen receptor modulators. Bioorg. Med. Chem. Lett. 17 (2007) 4487-4490
212. Manly J.J., Merchant C.A., Jacobs D.M., Small S., Bell K., Ferin M., and Mayeux R. Endogenous estrogen levels and Alzheimer's disease among postmenopausal women. Neurology 54 (2000) 833-837
213. Manthey D., Heck S., Engert S., and Behl C. Estrogen induces a rapid secretion of amyloid b precursor protein via the mitogen-activated protein kinase pathway. Eur. J. Biochem. 268 (2001) 4285-4291
214. 2+ homeostasis and cell death. J. Neurosci. 15 (1995) 6239-6249
215. 2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 65 (1995) 1740-1751
216. Mattson M.P., Partin J., and Begley J.G. Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites. Brain Res. 807 (1998) 167-176
217. Meier D.E., Orwoll E.S., Keenan E.J., and Fagerstrom R.M. Marked decline in trabecular bone mineral content in healthy men with age: lack of association with sex steroid levels. J. Am. Geriatr. Soc. 35 (1987) 189-197
218. Mize A.L., Young L.J., and Alper R.H. Uncoupling of 5-HT1A receptors in the brain by estrogens: regional variations in antagonism by ICI 182,780. Neuropharmacology 44 (2003) 584-591
219. Moffat S.D., Zonderman A.B., Metter E.J., Blackman M.R., Harman S.M., and Resnick S.M. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J. Clin. Endocrnol. Metab. 87 (2002) 5001-5007
220. Moffat S.D., Zonderman A.B., Metter E.J., Kawas C., Blackman M.R., Harman S.M., and Resnick S.M. Free testosterone and risk for Alzheimer disease in older men. Neurology 62 (2004) 188-193
221. Molsa P.K., Marttila R.J., and Rinne U.K. Epidemiology of dementia in a Finnish population. Acta Neurol. Scand. 65 (1982) 541-552
222. Mook-Jung I., Joo I., Sohn S., Kwon H.J., Huh K., and Jung M.W. Estrogen blocks neurotoxic effects of beta-amyloid (1-42) and induces neurite extension on B103 cells. Neurosci. Lett. 235 (1997) 101-104
223. Morali G., Lemus A.E., Munguia R., Arteaga M., Perez-Palacios G., Sundaram K., Kumar N., and Bardin C.W. Induction of male sexual behavior in the rat by 7 alpha-methyl-19-nortestosterone, an androgen that does not undergo 5 alpha-reduction. Biol. Reprod. 49 (1993) 577-581
224. Morley J.E. Androgens and aging. Maturitas 38 (2001) 61-71 discussion 71-63
225. Morley J.E., and Perry H.M. Androgen treatment of male hypogonadism in older males. J. Steroid Biochem. Mol. Biol. 85 (2003) 367-373
226. Morley J.E., Kaiser F.E., Perry H.M., Patrick P., Morley P.M., Stauber P.M., Vellas B., Baumgartner R.N., and Garry P.J. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabol.: Clin. Exp. 46 (1997) 410-413
227. Muller M., den Tonkelaar I., Thijssen J.H., Grobbee D.E., and van der Schouw Y.T. Endogenous sex hormones in men aged 40-80 years. Eur. J. Endocrinol. 149 (2003) 583-589
228. Mulnard R.A., Cotman C.W., Kawas C., van Dyck C.H., Sano M., Doody R., Koss E., Pfeiffer E., Jin S., Gamst A., Grundman M., Thomas R., and Thal L.J. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. J. Am. Med. Assoc. 283 (2000) 1007
229. Nguyen T.V.V., Yao M., and Pike C.J. Androgens activate mitogen-activated protein kinase signaling: role in neuroprotection. J. Neurochem. 94 (2005) 1639-1651
230. 2+ elevation in human cultured prostatic stromal cells. Prostate 67 (2007) 74-82
231. Nguyen T.V., Yao M., and Pike C.J. Flutamide and cyproterone acetate exert agonist effects: induction of androgen receptor-dependent neuroprotection. Endocrinology 148 (2007) 2936-2943
232. Nilsen J., and Brinton R.D. Impact of progestins on estradiol potentiation of the glutamate calcium response. Neuroreport 13 (2002) 825-830
233. Nilsen J., and Brinton R.D. Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling. Proc. Natl. Acad. Sci. USA 100 (2003) 10506-10511
234. Nilsen J., and Diaz_Brinton R. Mechanism of estrogen-mediated neuroprotection: regulation of mitochondrial calcium and Bcl-2 expression. Proc. Natl. Acad. Sci. USA 100 (2003) 2842-2847
235. Nilsen J., Mor G., and Naftolin F. Raloxifene induces neurite outgrowth in estrogen receptor positive PC12 cells. Menopause 5 (1998) 211-216
236. Nilsen J., Chen S., and Brinton R.D. Dual action of estrogen on glutamate-induced calcium signaling: mechanisms requiring interaction between estrogen receptors and src/mitogen activated protein kinase pathway. Brain Res. 930 (2002) 216-234
237. Nordell V.L., Scarborough M.M., Buchanan A.K., and Sohrabji F. Differential effects of estrogen in the injured forebrain of young adult and reproductive senescent animals. Neurobiol. Aging 24 (2003) 733-743
238. Oddo S., Caccamo A., Kitazawa M., Tseng B.P., and LaFerla F.M. Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. Neurobiol. Aging 24 (2003) 1063-1070
239. Effects of Estrogen or Estrogen/Progestin Regimens on Heart Disease Risk Factors in Postmenopausal Women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial, Jama 273 (1995) 199-208.
240. Ogiue-Ikeda M., Tanabe N., Mukai H., Hojo Y., Murakami G., Tsurugizawa T., Takata N., Kimoto T., and Kawato S. Rapid modulation of synaptic plasticity by estrogens as well as endocrine disrupters in hippocampal neurons. Brain Res. Rev. 57 (2008) 363-375
241. Ohkura T., Isse K., Akazawa K., Hamamoto M., Yaoi Y., and Hagino N. Evaluation of estrogen treatment in female patients with dementia of the Alzheimer type. Endocr. J. 41 (1994) 361-371
242. Olariu A., Yamada K., and Nabeshima T. Amyloid pathology and protein kinase C (PKC): possible therapeutics effects of PKC activators. J. Pharmacol. Sci. 97 (2005) 1-5
243. O'Neill K., Chen S., and Brinton R.D. Impact of the selective estrogen receptor modulator, raloxifene, on neuronal survival and outgrowth following toxic insults associated with aging and Alzheimer's disease. Exp. Neurol. 185 (2004) 63-80
244. Orlando R., Caruso A., Molinaro G., Motolese M., Matrisciano F., Togna G., Melchiorri D., Nicoletti F., and Bruno V. Nanomolar concentrations of anabolic-androgenic steroids amplify excitotoxic neuronal death in mixed mouse cortical cultures. Brain Res. 1165 (2007) 21-29
245. Ostrowski J., Kuhns J.E., Lupisella J.A., Manfredi M.C., Beehler B.C., Krystek Jr. S.R., Bi Y., Sun C., Seethala R., Golla R., Sleph P.G., Fura A., An Y., Kish K.F., Sack J.S., Mookhtiar K.A., Grover G.J., and Hamann L.G. Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats. Endocrinology 148 (2007) 4-12
246. Paganini-Hill A., and Clark L.J. Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. Breast Cancer Res. Treat 64 (2000) 165-176
247. Paganini-Hill A., and Henderson V.W. Estrogen deficiency and risk of Alzheimer's disease in women. Am. J. Epidemiol. 140 (1994) 256-261
248. Paganini-Hill A., and Henderson V.W. Estrogen replacement therapy and risk of Alzheimer disease. Arch. Intern. Med. 156 (1996) 2213-2217
249. Paoletti A.M., Congia S., Lello S., Tedde D., Orru M., Pistis M., Pilloni M., Zedda P., Loddo A., and Melis G.B. Low androgenization index in elderly women and elderly men with Alzheimer's disease. Neurology 62 (2004) 301-303
250. Papasozomenos S.C. The heat shock-induced hyperphosphorylation of tau is estrogen-independent and prevented by androgens: implications for Alzheimer disease. Proc. Natl. Acad. Sci. USA 94 (1997) 6612-6617
251. Papasozomenos S.C., and Papasozomenos T. Androgens prevent the heat shock-induced hyperphosphorylation but not dephosphorylation of t in female rats. implications for Alzheimer's disease. J. Alzheimers Dis. 1 (1999) 147-153
252. Papasozomenos S., and Shanavas A. Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3 beta but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of tau: implications for Alzheimer's disease. Proc. Natl. Acad. Sci. USA 99 (2002) 1140-1145
253. Park S.Y., Tournell C., Sinjoanu R.C., and Ferreira A. Caspase-3- and calpain-mediated tau cleavage are differentially prevented by estrogen and testosterone in beta-amyloid-treated hippocampal neurons. Neuroscience 144 (2007) 119-127
254. Patrone C., Andersson S., Korhonen L., and Lindholm D. Estrogen receptor-dependent regulation of sensory neuron survival in developing dorsal root ganglion. Proc. Natl. Acad. Sci. USA 96 (1999) 10905-10910
255. Pennanen C., Kivipelto M., Tuomainen S., Hartikainen P., Hanninen T., Laakso M.P., Hallikainen M., Vanhanen M., Nissinen A., Helkala E.L., Vainio P., Vanninen R., Partanen K., and Soininen H. Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol. Aging 25 (2004) 303-310
256. Perillo B., Sasso A., Abbondanza C., and Palumbo G. 17beta-estradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements present in the coding sequence. Mol. Cell Biol. 20 (2000) 2890-2901
257. Persson I., Adami H.O., Bergkvist L., Lindgren A., Pettersson B., Hoover R., and Schairer C. Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study. Bmj 298 (1989) 147-151
258. Petanceska S.S., Nagy V., Frail D., and Gandy S. Ovariectomy and 17beta-estradiol modulate the levels of Alzheimer's amyloid beta peptides in brain. Exp. Gerontol. 35 (2000) 1317-1325
259. Pike C.J. Estrogen modulates neuronal Bcl-xL expression and beta-amyloid-induced apoptosis: relevance to Alzheimer's disease. J. Neurochem. 72 (1999) 1552-1563
260. Pike C.J. Testosterone attenuates beta-amyloid toxicity in cultured hippocampal neurons. Brain Res. 919 (2001) 160-165
261. Pike C.J., Walencewicz A.J., Glabe C.G., and Cotman C.W. Aggregation-related toxicity of synthetic beta-amyloid protein in hippocampal cultures. Eur. J. Pharmacol. 207 (1991) 367-368
262. Pike C.J., Cummings B.J., and Cotman C.W. beta-Amyloid induces neuritic dystrophy in vitro: similarities with Alzheimer pathology. Neuroreport 3 (1992) 769-772
263. Pike C.J., Burdick D., Walencewicz A.J., Glabe C.G., and Cotman C.W. Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J. Neurosci. 13 (1993) 1676-1687
264. Pike C.J., Cummings B.J., Monzavi R., and Cotman C.W. Beta-amyloid-induced changes in cultured astrocytes parallel reactive astrocytosis associated with senile plaques in Alzheimer's disease. Neuroscience 63 (1994) 517-531
265. Pinkerton J.V., and Henderson V.W. Estrogen and cognition, with a focus on Alzheimer's disease. Semin. Reprod. Med. 23 (2005) 172-179
266. Polo-Kantola P., Portin R., Polo O., Helenius H., Irjala K., and Erkkola R. The effect of short-term estrogen replacement therapy on cognition: a randomized, double-blind, cross-over trial in postmenopausal women. Obstet. Gynecol. 91 (1998) 459-466
267. Pow D.V., Perry V.H., Morris J.F., and Gordon S. Microglia in the neurohypophysis associate with and endocytose terminal portions of neurosecretory neurons. Neuroscience 33 (1989) 567-578
268. Qiu J., Bosch M.A., Tobias S.C., Grandy D.K., Scanlan T.S., Ronnekleiv O.K., and Kelly M.J. Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C. J. Neurosci. 23 (2003) 9529-9540
269. J. Raber, Androgens, apoE, and Alzheimer's disease, Sci. Aging Knowledge Environ. 2004 (2004) re2.
270. Raber J. AR, apoE, and cognitive function. Horm. Behav. 53 (2008) 706-715
271. Ramsden M., Nyborg A.C., Murphy M.P., Chang L., Stanczyk F.Z., Golde T.E., and Pike C.J. Androgens modulate beta-amyloid levels in male rat brain. J. Neurochem. 87 (2003) 1052-1055
272. Ramsden M., Shin T.M., and Pike C.J. Androgens modulate neuronal vulnerability to kainate lesion. Neuroscience 122 (2003) 573-578
273. Rapp S.R., Espeland M.A., Shumaker S.A., Henderson V.W., Brunner R.L., Manson J.E., Gass M.L., Stefanick M.L., Lane D.S., Hays J., Johnson K.C., Coker L.H., Dailey M., and Bowen D. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. Jama: J. Am. Med. Assoc. 289 (2003) 2663-2672
274. Rasmuson S., Nasman B., Carlstrom K., and Olsson T. Increased levels of adrenocortical and gonadal hormones in mild to moderate Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 13 (2002) 74-79
275. Regan R.F., and Guo Y. Estrogens attenuate neuronal injury due to hemoglobin, chemical hypoxia, and excitatory amino acids in murine cortical cultures. Brain Res. 764 (1997) 133-140
276. Resnick S.M., and Henderson V.W. Hormone therapy and risk of Alzheimer disease: a critical time. Jama 288 (2002) 2170-2172
277. Rhodes M.E., and Frye C.A. Androgens in the hippocampus can alter, and be altered by, ictal activity. Pharmacol. Biochem. Behav. 78 (2004) 483-493
278. Rice-Evans C.A., Miller N.J., and Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Rad. Biol. Med. 20 (1996) 933-956
279. Rice-Evans C., Miller N., and Paganga G. Antioxidant properties of phenolic compounds. Trends Plant Sci. 2 (1997) 152-159
280. Riederer P., and Hoyer S. From benefit to damage. Glutamate and advanced glycation end products in Alzheimer brain. J. Neural. Transm. 113 (2006) 1671-1677
281. Rocca W.A., Amaducci L.A., and Schoenberg B.S. Epidemiology of clinically diagnosed Alzheimer's disease. Ann. Neurol. 19 (1986) 415-424
282. Rogers J., Strohmeyer R., Kovelowski C., and Li R.G. Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide. Glia 40 (2002) 260-269
283. Rosario E.R., and Pike C.J. Androgen regulation of beta-amyloid protein and the risk of Alzheimer's disease. Brain Res. Rev. 57 (2008) 444-453
284. Rosario E.R., Chang L., Stanczyk F.Z., and Pike C.J. Age-related testosterone depletion and the development of Alzheimer disease. Jama 292 (2004) 1431-1432
285. Rosario E.R., Carroll J.C., Oddo S., LaFerla F.M., and Pike C.J. Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J. Neurosci. 26 (2006) 13384-13389
286. Rosario E.R., Ramsden M., and Pike C.J. Progestins inhibit the neuroprotective effects of estrogen in rat hippocampus. Brain Res. 1099 (2006) 206-210
287. E.R. Rosario, L. Chang, E.H. Head, F. Z. Stanczyk, C. J. Pike, Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease, Neurobiol. Aging, in press.
288. Rowan M.J., Klyubin I., Wang Q., Hu N.W., and Anwyl R. Synaptic memory mechanisms: Alzheimer's disease amyloid beta-peptide-induced dysfunction. Biochem. Soc. Trans. 35 (2007) 1219-1223
289. Rubin B.S., Fox T.O., and Bridges R.S. Estrogen binding in nuclear and cytosolic extracts from brain and pituitary of middle-aged female rats. Brain Res. 383 (1986) 60-67
290. Ruitenberg A., Ott A., van Swieten J.C., Hofman A., and Breteler M.M.B. Incidence of dementia: does gender make a difference?. Neurobiol. Aging 22 (2001) 575-580
291. Sastre M., Walter J., and Gentleman S.M. Interactions between APP secretases and inflammatory mediators. J. Neuroinflammation 5 (2008) 25
292. Savaskan E., Olivieri G., Meier F., Ravid R., and Muller-Spahn F. Hippocampal estrogen beta-receptor immunoreactivity is increased in Alzheimer's disease. Brain Res. 908 (2001) 113-119
293. Schultz C., Braak H., and Braak E. A sex difference in neurodegeneration of the human hypothalamus. Neurosci. Lett. 212 (1996) 103-106
294. Schultz C., Ghebremedhin E., Braak E., and Braak H. Sex-dependent cytoskeletal changes of the human hypothalamus develop independently of Alzheimer's disease. Exp. Neurol. 160 (1999) 186-193
295. Schumacher M., Sitruk-Ware R., and De Nicola A.F. Progesterone and progestins: neuroprotection and myelin repair. Curr. Opin. Pharmacol. 8 (2008) 740-746
296. Schupf N., Lee J.H., Wei M., Pang D., Chace C., Cheng R., Zigman W.B., Tycko B., and Silverman W. Estrogen receptor-alpha variants increase risk of Alzheimer's disease in women with Down syndrome. Dement. Geriatr. Cogn. Disord. 25 (2008) 476-482
297. Selkoe D.J., Yamazaki T., Citron M., Podlisny M.B., Koo E.H., Teplow D.B., and Haass C. The role of APP processing and trafficking pathways in the formation of amyloid beta-protein. Ann. NY Acad. Sci. 777 (1996) 57-64
298. Selvamani A., and Sohrabji F. Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats. Neurobiol. Aging (2008)
299. Sétáló G., Singh M., Nethrapalli I.S., and Toran-Allerand C.D. Protein kinase C activity is necessary for estrogen-induced Erk phosphorylation in neocortical explants. J. Neurochem. Res. 30 (2005) 779-790
300. Shang Y., and Brown M. Molecular determinants for the tissue specificity of SERMs. Science 295 (2002) 2465-2468
301. Shao T.C., Li H.L., Kasper S., Matusik R., Ittmann M., and Cunningham G.R. Comparison of the growth-promoting effects of testosterone and 7-alpha-methyl-19-nor-testosterone (MENT) on the prostate and levator ani muscle of LPB-tag transgenic mice. Prostate 66 (2006) 369-376
302. Sheffield-Moore M., and Urban R.J. An overview of the endocrinology of skeletal muscle. Trends Endocrinol. Metab. 15 (2004) 110-115
303. Sheldahl L.C., Marriott L.K., Bryant D.M., Shapiro R.A., and Dorsa D.M. Neuroprotective effects of estrogen and selective estrogen receptor modulators begin at the plasma membrane. Minerva Endocrinol. 32 (2007) 87-94
304. Shen R., Sumitomo M., Dai J., Hardy D.O., Navarro D., Usmani B., Papandreou C.N., Hersh L.B., Shipp M.A., Freedman L.P., and Nanus D.M. Identification and characterization of two androgen response regions in the human neutral endopeptidase gene. Mol. Cell Endocrinol. 170 (2000) 131-142
305. Sherwin B.B. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology 13 (1988) 345-357
306. Sherwin B.B. Estrogen and cognitive functioning in women. Endocr. Rev. 24 (2003) 133-151
307. Shi J., Panickar K.S., Yang S.-H., Rabbani O., Day A.L., and Simpkins J.W. Estrogen attenuates over-expression of b-amyloid precursor protein messager RNA in an animal model of focal ischemia. Brain Res. 810 (1998) 87-92
308. Shilling V., Jenkins V., Fallowfield L., and Howell T. The effects of hormone therapy on cognition in breast cancer. J. Steroid Biochem. Mol. Biol. 86 (2003) 405-412
309. Shughrue P.J., and Merchenthaler I. Estrogen is more than just a "Sex Hormone": novel sites for estrogen action in the hippocampus and cerebral cortex. Front. Neuroendocrinol. 21 (2000) 95-101
310. Shughrue P.J., Lane M.V., and Merchenthaler I. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J. Comp. Neurol. 388 (1997) 507-525
311. Shumaker S.A., Legault C., Rapp S.R., Thal L., Wallace R.B., Ockene J.K., Hendrix S.L., Jones B.N., Assaf A.R., Jackson R.D., Kotchen J.M., Wassertheil_Smoller S., and Wactawski_Wende J. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. Jama: J. Am. Med. Assoc. 289 (2003) 2651-2662
312. Shumaker S.A., Legault C., Kuller L., Rapp S.R., Thal L., Lane D.S., Fillit H., Stefanick M.L., Hendrix S.L., Lewis C.E., Masaki K., and Coker L.H. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. Jama 291 (2004) 2947-2958
313. Silva I., Mello L.E., Freymuller E., Haidar M.A., and Baracat E.C. Estrogen, progestogen and tamoxifen increase synaptic density of the hippocampus of ovariectomized rats. Neurosci. Lett. 291 (2000) 183-186
314. Simerly R.B., Chang C., Muramatsu M., and Swanson L.W. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J. Comp. Neurol. 294 (1990) 76-95
315. Singer C.A., Rogers K.L., Strickland T.M., and Dorsa D.M. Estrogen protects primary cortical neurons from glutamate toxicity. Neurosci. Lett. 212 (1996) 13-16
316. Singer C.A., Rogers K.L., and Dorsa D.M. Modulation of Bcl-2 expression: a potential component of estrogen protection in NT2 neurons. Neuroreport 9 (1998) 2565-2568
317. Singer C.A., Figueroa_Masot X.A., Batchelor R.H., and Dorsa D.M. The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J. Neurosci.: Official J. Soc. Neurosci. 19 (1999) 2455-2463
318. Singh M. Ovarian hormones elicit phosphorylation of Akt and extracellular-signal regulated kinase in explants of the cerebral cortex. Endocrine 14 (2001) 407-415
319. Singh M., Setalo Jr. G., Guan X., Warren M., and Toran-Allerand C.D. Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: convergence of estrogen and neurotrophin
320. Stoltzner S.E., Berchtold N.C., Cotman C.W., and Pike C.J. Estrogen regulates Bcl-x expression in rat hippocampus. Neuroreport 12 (2001) 2797-2800
321. Stone D.J., Rozovsky I., Morgan T.E., Anderson C.P., Lopez L.M., Shick J., and Finch C.E. Effects of age on gene expression during estrogen-induced synaptic sprouting in the female rat. Exp. Neurol. 165 (2000) 46-57
322. Strittmatter W.J., and Roses A.D. Apolipoprotein E and Alzheimer disease. Proc. Natl. Acad. Sci. USA 92 (1995) 4725-4727
323. Struble R.G., Nathan B.P., Cady C., Cheng X., and McAsey M. Estradiol regulation of astroglia and apolipoprotein E: an important role in neuronal regeneration. Exp. Gerontol. 42 (2007) 54-63
324. Subbiah M.T., Kessel B., Agrawal M., Rajan R., Abplanalp W., and Rymaszewski Z. Antioxidant potential of specific estrogens on lipid peroxidation. J. Clin. Endocrinol. Metab. 77 (1993) 1095-1097
325. Sugioka K., Shimosegawa Y., and Nakano M. Estrogens as natural antioxidants of membrane phospholipid peroxidation. FEBS Lett. 210 (1987) 37-39
326. Swerdloff R.S., and Wang C. Androgen deficiency and aging in men. Western J. Med. 159 (1993) 579-585
327. Tan R.S., and Culberson J.W. An integrative review on current evidence of testosterone replacement therapy for the andropause. Maturitas 45 (2003) 15-27
328. Tan R.S., and Pu S.J. A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease. Aging Male 6 (2003) 13
329. Tang M.X., Jacobs D., Stern Y., Marder K., Schofield P.R., Gurland B., Andrews H., and Mayeux R. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. The Lancet 348 (1996) 429
330. Tanzer L., and Jones K.J. Gonadal steroid regulation of hamster facial nerve regeneration: effects of dihydrotestosterone and estradiol. Exp. Neurol. 146 (1997) 258-264
331. Tanzi R.E., Moir R.D., and Wagner S.L. Clearance of Alzheimer's A[beta] Peptide: the many roads to perdition. Neuron 43 (2004) 605-608
332. Tariq S.H., Haren M.T., Kim M.J., and Morley J.E. Andropause: is the emperor wearing any clothes?. Rev. Endocr. Metab. Disord. 6 (2005) 77-84
333. Thakur M.K., and Mani S.T. Estradiol regulates APP mRNA alternative splicing in the mice brain cortex. Neurosci. Lett. 381 (2005) 154-157
334. Thomas T., Bryant M., Clark L., Garces A., and Rhodin J. Estrogen and raloxifene activities on amyloid - induced inflammatory reaction. Microvasc. Res. 61 (2001) 28-39
335. Toran-Allerand C.D., Singh M., and Sétáló G. Novel mechanisms of estrogen action in the brain: new players in an old story. Front. Neuroendocrinol. 20 (1999) 97-121
336. Turner P.R., O'Connor K., Tate W.P., and Abraham W.C. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog. Neurobiol. 70 (2003) 1-32
337. Vardy E.R.L.C., Catto A.J., and Hooper N.M. Proteolytic mechanisms in amyloid-[beta] metabolism: therapeutic implications for Alzheimer's disease. Trends Mol. Med. 11 (2005) 464-472
338. Vasto S., Candore G., Listi F., Balistreri C.R., Colonna-Romano G., Malavolta M., Lio D., Nuzzo D., Mocchegiani E., Di Bona D., and Caruso C. Inflammation, genes and zinc in Alzheimer's disease. Brain Res. Rev. 58 (2008) 96-105
339. Vaughan C., Goldstein F.C., and Tenover J.L. Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone. J. Androl. 28 (2007) 875-882
340. Vedder H., Anthes N., Stumm G., Wurz C., Behl C., and Krieg J.-C. Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system. J. Neurochem. 72 (1999) 2531-2538
341. Vegeto E., Bonincontro C., Pollio G., Sala A., Viappiani S., Nardi F., Brusadelli A., Viviani B., Ciana P., and Maggi A. Estrogen prevents the lipopolysaccharide-induced inflammatory response in microglia. J. Neurosci. 21 (2001) 1809-1818
342. Venken K., Boonen S., Van Herck E., Vandenput L., Kumar N., Sitruk-Ware R., Sundaram K., Bouillon R., and Vanderschueren D. Bone and muscle protective potential of the prostate-sparing synthetic androgen 7alpha-methyl-19-nortestosterone: evidence from the aged orchidectomized male rat model. Bone 36 (2005) 663-670
343. Verdile G., Fuller S., Atwood C.S., Laws S.M., Gandy S.E., and Martins R.N. The role of beta amyloid in Alzheimer's disease: still a cause of everything or the only one who got caught?. Pharmacol. Res. 50 (2004) 397-409
344. Vincent B., and Smith J.D. Effect of estradiol on neuronal Swedish-mutated beta-amyloid precursor protein metabolism: reversal by astrocytic cells. Biochem. Biophys/Res. Commun. 271 (2000) 82-85
345. von Eckardstein S., Noe G., Brache V., Nieschlag E., Croxatto H., Alvarez F., Moo-Young A., Sivin I., Kumar N., Small M., and Sundaram K. A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men. J. Clin Endocrinol. Metab. 88 (2003) 5232-5239
346. Wahjoepramono E.J., Wijaya L.K., Taddei K., Martins G., Howard M., Ruyck K.d., Bates K., Dhaliwald S.S., Verdile G., Carruthers M., and Martins R.N. Distinct effects of testosterone on plasma and cerebrospinal fluid amyloid-b levels. J. Alzheimer's Dis. 129 (2008) 129-137
347. Walsh D., and Selkoe D. A beta oligomers - a decade of discovery. J. Neurochem. 101 (2007) 1172-1184
348. Walsh D.M., Klyubin I., Fadeeva J.V., Rowan M.J., and Selkoe D.J. Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition. Biochem. Soc. Trans. 30 (2002) 552-557
349. Wang P.N., Liao S.Q., Liu R.S., Liu C.Y., Chao H.T., Lu S.R., Yu H.Y., Wang S.J., and Liu H.C. Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology 54 (2000) 2061-2066
350. Wang J., Tanila H., Puolivali J., Kadish I., and van Groen T. Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice. Neurobiol. Dis. 14 (2003) 318-327
351. Waring S.C., Rocca W.A., Petersen R.C., O_Brien P.C., Tangalos E.G., and Kokmen E. Postmenopausal estrogen replacement therapy and risk of AD: a population-based study. Neurology 52 (1999) 965-970
352. Watanabe T., Koba S., Kawamura M., Itokawa M., Idei T., Nakagawa Y., Iguchi T., and Katagiri T. Small dense low-density lipoprotein and carotid atherosclerosis in relation to vascular dementia. Metabolism 53 (2004) 476-482
353. Watters J.J., Campbell J.S., Cunningham M.J., Krebs E.G., and Dorsa D.M. Rapid membrane effects of steroids in neuroblastoma cells: effects of estrogen on mitogen activated protein kinase signalling cascade and c-fos immediate early gene transcription. Endocrinology 138 (1997) 4030-4033
354. Weaver Jr. C.E., Park-Chung M., Gibbs T.T., and Farb D.H. 17beta-Estradiol protects against NMDA-induced excitotoxicity by direct inhibition of NMDA receptors. Brain Res. 761 (1997) 338-341
355. Weaver C.L., Espinoza M., Kress Y., and Davies P. Conformational change as one of the earliest alterations of tau in Alzheimer's disease. Neurobiol. Aging 21 (2000) 719-727
356. 2+ channel blockers attenuate beta-amyloid peptide toxicity to cortical neurons in culture. J. Neurochem. 62 (1994) 372-375
357. Wharton W., Brinton E., Cedars M., Lobo R.A., Manson J., Merriam G.R., Miller V.M., Santoro N., Taylor H.S., Harman S.M., and Asthana S. Baseline cognitive and demographic characteristics of women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) Alzheimer's & Dementia. J. Alzheimer's Assoc. 4 (2008) T792
358. Wilhelmsen K.C., Clark L.N., Miller B.L., and Geschwind D.H. Tau mutations in frontotemporal dementia. Dement. Geriatr. Cogn. Disord. 10 Suppl. 1 (1999) 88-92
359. Wilson E.M. Muscle-bound? A tissue-selective nonsteroidal androgen receptor modulator. Endocrinology 148 (2007) 1-3
360. Wise P.M. Estrogen therapy: does it help or hurt the adult and aging brain? Insights derived from animal models. Neuroscience 138 (2006) 831-835
361. Wise P.M., and Parsons B. Nuclear estradiol and cytosol progestin receptor concentrations in the brain and the pituitary gland and sexual behavior in ovariectomized estradiol-treated middle-aged rats. Endocrinology 115 (1984) 810-816
362. Woolley C.S., and McEwen B.S. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J. Comp. Neurol. 336 (1993) 293-306
363. Wu X., Glinn M.A., Ostrowski N.L., Su Y., Ni B., Cole H.W., Bryant H.U., and Paul S.M. Raloxifene and estradiol benzoate both fully restore hippocampal choline acetyltransferase activity in ovariectomized rats. Brain Res. 847 (1999) 98-104
364. 2+ influx via L-type calcium channels activates the Src/ERK/cyclic-AMP response element binding protein signal pathway and BCL-2 expression in rat hippocampal neurons: a potential initiation mechanism for estrogen-induced neuroprotection. Neuroscience 135 (2005) 59-72
365. Z.-M. Xiao, L. Sun, Y.-M. Liu, J.-J. Zhang, J. Huang, Estrogen regulation of the neprilysin gene through a hormone-responsive element, J. Mol. Neurosci., in press.
366. Xu H., Gouras G.K., Greenfield J.P., Vincent B., Naslund J., Mazzarelli L., Fried G., Jovanovic J.N., Seeger M., Relkin N.R., Liao F., Checler F., Buxbaum J.D., Chait B.T., Thinakaran G., Sisodia S.S., Wang R., Greengard P., and Gandy S. Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nat. Med. 4 (1998) 447-451
367. Xu Y., Armstrong S.J., Arenas I.A., Pehowich D.J., and Davidge S.T. Cardioprotection by chronic estrogen or superoxide dismutase mimetic treatment in the aged female rat. Am. J. Physiol. Heart Circ. Physiol. 287 (2004) H165-H171
368. Xu H., Wang R., Zhang Y.-W., and Zhang X. Estrogen, -amyloid metabolism/trafficking, and Alzheimer's disease. Ann. NY Acad. Sci. 1089 (2006) 324-342
369. Yaffe K., Krueger K., Sarkar S., Grady D., Barrett-Connor E., Cox D.A., and Nickelsen T. The multiple outcomes of raloxifene evaluation investigators, cognitive function in postmenopausal women treated with raloxifene. New Engl. J. Med. 344 (2001) 1207-1213
370. Yaffe K., Krueger K., Cummings S.R., Blackwell T., Henderson V.W., Sarkar S., Ensrud K., and Grady D. Effect of raloxifene on prevention of dementia and cognitive impairment in older women: the Multiple Outcomes of Raloxifene Evaluation (MORE) randomized trial. Am. J. Psychiatry 162 (2005) 683-690
371. Yang S.H., Perez E., Cutright J., Liu R., He Z., Day A.L., and Simpkins J.W. Testosterone increases neurotoxicity of glutamate in vitro and ischemia-reperfusion injury in an animal model. J. Appl. Physiol. 92 (2002) 195-201
372. Yang S.H., Liu R., Wen Y., Perez E., Cutright J., Brun-Zinkernagel A.M., Singh M., Day A.L., and Simpkins J.W. Neuroendocrine mechanism for tolerance to cerebral ischemia-reperfusion injury in male rats. J. Neurobiol. 62 (2005) 341-351
373. Yankner B.A., and Lu T. Amyloid {beta}-Protein Toxicity and the Pathogenesis of Alzheimer Disease. J. Biol. Chem. 284 (2009) 4755-4759
374. Yao M., Nguyen T.V., and Pike C.J. Beta-amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w. J. Neurosci. 25 (2005) 1149-1158
375. Yao M., Nguyen T.V., and Pike C.J. Estrogen regulates Bcl-w and Bim expression: role in protection against beta-amyloid peptide-induced neuronal death. J. Neurosci. 27 (2007) 1422-1433
376. Yao M., Nguyen T.V., Rosario E.R., Ramsden M., and Pike C.J. Androgens regulate neprilysin expression: role in reducing beta-amyloid levels. J. Neurochem. (2008)
377. Yu W.H. Effect of testosterone on the regeneration of the hypoglossal nerve in rats. Exp. Neurol. 77 (1982) 129-141
378. Yu W.H. Administration of testosterone attenuates neuronal loss following axotomy in the brain-stem motor nuclei of female rats. J. Neurosci. 9 (1989) 3908-3914
379. Yu W.H., and Srinivasan R. Effect of testosterone and 5 alpha-dihydrotestosterone on regeneration of the hypoglossal nerve in rats. Exp. Neurol. 71 (1981) 431-435
380. Yue X., Lu M., Lancaster T., Cao P., Honda S.-I., Staufenbiel M., Harada N., Zhong Z., Shen Y., and Li R. Brain estrogen deficiency accelerates Ab plaque formation in an Alzheimer's disease animal model. Proc. Natl. Acad. Sci. 102 (2005) 19198-19203
381. Yune T.Y., Park H.G., Lee J.Y., and Oh T.H. Estrogen-induced Bcl-2 expression after spinal cord injury is mediated through phosphoinositide-3-kinase/Akt-dependent CREB activation. J. Neurotrauma. 25 (2008) 1121-1131
382. Zandi P.P., Carlson M.C., Plassman B.L., Welsh-Bohmer K.A., Mayer L.S., Steffens D.C., and Breitner J.C.S. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. J. Am. Med. Assoc. 288 (2002) 2123-2129
383. Zhang L., Rubinow D.R.C.A., Xaing G.-q., Li B.-S., Chang Y.H., Maric D., Barker J.L., and Ma W. Estrogen protects against b-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt. Neuroreport 12 (2001) 1919-1923
384. Zhang Y., Champagne N., Beitel L.K., Goodyer C.G., Trifiro M., and LeBlanc A. Estrogen and androgen protection of human neurons against intracellular amyloid beta(1-42) toxicity through heat shock protein 70. J. Neurosci. 24 (2004) 5315-5321
385. Zhang S., Huang Y., Zhu Y.C., and Yao T. Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway. Acta Pharmacol. Sin. 26 (2005) 171-176
386. Zhang Q.G., Wang R., Khan M., Mahesh V., and Brann D.W. Role of Dickkopf-1, an antagonist of the Wnt/beta-catenin signaling pathway, in estrogen-induced neuroprotection and attenuation of tau phosphorylation. J. Neurosci. 28 (2008) 8430-8441
387. Zhao L., and Brinton R.D. Estrogen receptor alpha and beta differentially regulate intracellular Ca(2+) dynamics leading to ERK phosphorylation and estrogen neuroprotection in hippocampal neurons. Brain Res. 1172 (2007) 48-59
388. Zhao L., Wu T.W., and Brinton R.D. Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased Bcl-2 expression in primary hippocampal neurons. Brain Res. 1010 (2004) 22-34
389. Zhao L., Jin C., Mao Z., Gopinathan M.B., Rehder K., and Brinton R.D. Design, synthesis, and estrogenic activity of a novel estrogen receptor modulator - a hybrid structure of 17beta-estradiol and vitamin E in hippocampal neurons. J. Med. Chem. 50 (2007) 4471-4481
390. Zheng H., Xu H., Uljon S.N., Gross R., Hardy K., Gaynor J., Lafrancois J., Simpkins J., Refolo L.M., Petanceska S., Wang R., and Duff K. Modulation of A(beta) peptides by estrogen in mouse models. J. Neurochem. 80 (2002) 191-196