期刊论文详细信息
Biology of Sex Differences
Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?
Kurtresha Worden1  Lauren Broestl1  Dena B Dubal1 
[1]Laboratory of Neuroscience and Aging Research, Department of Neurology, Sandler Neurosciences Center, Room 212B, University of California, San Francisco, San Francisco, CA 94158, USA
关键词: Andropause;    Menopause;    Reproductive aging;    Aging;    Human;    Mouse;    Transgenic;    Pathology;    Behavior;    Cognition;    Androgens;    Testosterone;    Progesterone;    Estrogen;    Hormones;    Sex chromosomes;    Neurodegeneration;    Tau;    ;    Alzheimer’s disease;    Brain;    Gender;    Sex;   
Others  :  793407
DOI  :  10.1186/2042-6410-3-24
 received in 2012-08-09, accepted in 2012-09-27,  发布年份 2012
PDF
【 摘 要 】

Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer’s – and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer’s disease (AD) with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases.

【 授权许可】

   
2012 Dubal et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140705051327682.pdf 830KB PDF download
Figure 6. 46KB Image download
Figure 5. 41KB Image download
Figure 4. 47KB Image download
Figure 3. 57KB Image download
Figure 2. 48KB Image download
Figure 1. 29KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]Pankevich DE, Wizemann TM, Altevogt BM, Institute of Medicine (U.S.): Forum on Neuroscience and Nervous System Disorders. In Sex differences and implications for translational neuroscience research: workshop summary. D.C: National Academies Press, Washington; 2011.
  • [2]Wimo A, Prince M: World Alzheimer Report 2010: the global economic impact of dementia. In Book World Alzheimer Report 2010: the global economic impact of dementia. Alzheimer’s Disease International (ADI); 2010:1-56.
  • [3]Lindner MD, McArthur RA, Deadwyler SA, Hampson RE, Tariot PN: Chapter 4: Development, Optimization and Use of Preclinical Behavioral Models to Maximize the Productivity of Drug Discovery for Alzheimer's Disease. In Animal and Translational Models for CNS Drug Discovery. Volume 2: Neurological Disorders. Edited by McArthur R, Borsini F. San Diego: Academic Press; 2008:93-157.
  • [4]Becker RE, Greig NH, Giacobini E: Why do so many drugs for Alzheimer's disease fail in development? Time for new methods and new practices? J Alzheimers Dis 2008, 15:303-325.
  • [5]Huang Y, Mucke L: Alzheimer mechanisms and therapeutic strategies. Cell 2012, 148:1204-1222.
  • [6]Palop JJ, Chin J, Mucke L: A network dysfunction perspective on neurodegenerative diseases. Nature 2006, 443:768-773.
  • [7]Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R: Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991, 30:572-580.
  • [8]DeKosky ST, Scheff SW: Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 1990, 27:457-464.
  • [9]Pievani M, de Haan W, Wu T, Seeley WW, Frisoni GB: Functional network disruption in the degenerative dementias. Lancet Neurol 2011, 10:829-843.
  • [10]Palop JJ, Mucke L: Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nat Neurosci 2010, 13:812-818.
  • [11]Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR: Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 2003, 60:1495-1500.
  • [12]Villemagne VL, Ataka S, Mizuno T, Brooks WS, Wada Y, Kondo M, Jones G, Watanabe Y, Mulligan R, Nakagawa M, et al.: High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Arch Neurol 2009, 66:1537-1544.
  • [13]Furst AJ, Rabinovici GD, Rostomian AH, Steed T, Alkalay A, Racine C, Miller BL, Jagust WJ: Cognition, glucose metabolism and amyloid burden in Alzheimer's disease. Neurobiol Aging 2012, 33:215-225.
  • [14]Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P, Renbing X, Peck A: Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 1988, 23:138-144.
  • [15]Tomlinson BE, Blessed G, Roth M: Observations on the brains of non-demented old people. J Neurol Sci 1968, 7:331-356.
  • [16]Davis DG, Schmitt FA, Wekstein DR, Markesbery WR: Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 1999, 58:376-388.
  • [17]Crystal HA, Dickson DW, Sliwinski MJ, Lipton RB, Grober E, Marks-Nelson H, Antis P: Pathological markers associated with normal aging and dementia in the elderly. Ann Neurol 1993, 34:566-573.
  • [18]Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman DM, Bacskai BJ, Hyman BT: Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 2008, 451:720-724.
  • [19]Meyer-Luehmann M, Mielke M, Spires-Jones TL, Stoothoff W, Jones P, Bacskai BJ, Hyman BT: A reporter of local dendritic translocation shows plaque- related loss of neural system function in APP-transgenic mice. J Neurosci 2009, 29:12636-12640.
  • [20]Spires-Jones TL, Kopeikina KJ, Koffie RM, de Calignon A, Hyman BT: Are tangles as toxic as they look? J Mol Neurosci 2011, 45:438-444.
  • [21]Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L: High-level neuronal expression of abeta 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 2000, 20:4050-4058.
  • [22]Klein WL, Krafft GA, Finch CE: Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum? Trends Neurosci 2001, 24:219-224.
  • [23]Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM: Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003, 39:409-421.
  • [24]Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, et al.: Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005, 309:476-481.
  • [25]Haroutunian V, Purohit DP, Perl DP, Marin D, Khan K, Lantz M, Davis KL, Mohs RC: Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. Arch Neurol 1999, 56:713-718.
  • [26]O'Leary JC 3rd, Li Q, Marinec P, Blair LJ, Congdon EE, Johnson AG, Jinwal UK, Koren J 3rd, Jones JR, Kraft C, et al.: Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener 2010, 5:45. BioMed Central Full Text
  • [27]Sydow A, Van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, Drexler D, Zhou L, Rune G, Mandelkow E, et al.: Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic Tau mutant. J Neurosci 2011, 31:2511-2525.
  • [28]Morris M, Maeda S, Vossel K, Mucke L: The many faces of tau. Neuron 2011, 70:410-426.
  • [29]Yaffe K, Barnes E: Chapter 9: Epidemiology and risk factors. In The Behavioral Neurology of Dementia. Edited by Miller BL, Boeve BF. New York: Cambridge University Press; 2009.
  • [30]Bertram L, Lill CM, Tanzi RE: The genetics of Alzheimer disease: back to the future. Neuron 2010, 68:270-281.
  • [31]Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993, 261:921-923.
  • [32]Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM: 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 1997, 278:1349-1356.
  • [33]Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O, Bullido MJ, Engelborghs S, De Deyn P, Berr C, et al.: APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry 2011, 16:903-907.
  • [34]Logue MW, Schu M, Vardarajan BN, Buros J, Green RC, Go RC, Griffith P, Obisesan TO, Shatz R, Borenstein A, et al.: A comprehensive genetic association study of Alzheimer disease in African Americans. Arch Neurol 2011, 68:1569-1579.
  • [35]Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, et al.: A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 2012.
  • [36]Tanzi RE, Bertram L: Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 2005, 120:545-555.
  • [37]Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ: Soluble Abeta oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci 2011, 31:6627-6638.
  • [38]Yu W, Lu B: Synapses and dendritic spines as pathogenic targets in Alzheimer's disease. Neural Plast 2012, 2012:247150.
  • [39]Zempel H, Thies E, Mandelkow E, Mandelkow EM: Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. J Neurosci 2010, 30:11938-11950.
  • [40]Palop JJ, Mucke L: Synaptic depression and aberrant excitatory network activity in Alzheimer's disease: two faces of the same coin? Neuromolecular Med 2010, 12:48-55.
  • [41]Claus JJ, van Gool WA, Teunisse S, Walstra GJ, Kwa VI, Hijdra A, Verbeeten B Jr, Koelman JH, Bour LJ, Ongerboer De Visser BW: Predicting survival in patients with early Alzheimer's disease. Dement Geriatr Cogn Disord 1998, 9:284-293.
  • [42]Ueki A, Shinjo H, Shimode H, Nakajima T, Morita Y: Factors associated with mortality in patients with early-onset Alzheimer's disease: a five-year longitudinal study. Int J Geriatr Psychiatry 2001, 16:810-815.
  • [43]Heyman A, Wilkinson WE, Hurwitz BJ, Helms MJ, Haynes CS, Utley CM, Gwyther LP: Early-onset Alzheimer's disease: clinical predictors of institutionalization and death. Neurology 1987, 37:980-984.
  • [44]Stern Y, Tang MX, Albert MS, Brandt J, Jacobs DM, Bell K, Marder K, Sano M, Devanand D, Albert SM, et al.: Predicting time to nursing home care and death in individuals with Alzheimer disease. JAMA 1997, 277:806-812.
  • [45]Lapane KL, Gambassi G, Landi F, Sgadari A, Mor V, Bernabei R: Gender differences in predictors of mortality in nursing home residents with AD. Neurology 2001, 56:650-654.
  • [46]Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA: Is the risk of developing Alzheimer's disease greater for women than for men? Am J Epidemiol 2001, 153:132-136.
  • [47]Petersen RC, Roberts RO, Knopman DS, Geda YE, Cha RH, Pankratz VS, Boeve BF, Tangalos EG, Ivnik RJ, Rocca WA: Prevalence of mild cognitive impairment is higher in men. The Mayo Clinic Study of Aging. Neurology 2010, 75:889-897.
  • [48]Ganguli M, Dodge HH, Shen C, DeKosky ST: Mild cognitive impairment, amnestic type: an epidemiologic study. Neurology 2004, 63:115-121.
  • [49]Koivisto K, Reinikainen KJ, Hanninen T, Vanhanen M, Helkala EL, Mykkanen L, Laakso M, Pyorala K, Riekkinen PJ Sr: Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland. Neurology 1995, 45:741-747.
  • [50]Luck T, Luppa M, Briel S, Matschinger H, Konig HH, Bleich S, Villringer A, Angermeyer MC, Riedel-Heller SG: Mild cognitive impairment: incidence and risk factors: results of the leipzig longitudinal study of the aged. J Am Geriatr Soc 2010, 58:1903-1910.
  • [51]Kivipelto M, Helkala EL, Hanninen T, Laakso MP, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A: Midlife vascular risk factors and late-life mild cognitive impairment: a population-based study. Neurology 2001, 56:1683-1689.
  • [52]Jorm AF, Jolley D: The incidence of dementia: a meta-analysis. Neurology 1998, 51:728-733.
  • [53]Roberts RO, Geda YE, Knopman DS, Cha RH, Pankratz VS, Boeve BF, Tangalos EG, Ivnik RJ, Rocca WA, Petersen RC: The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging. Neurology 2012, 78:342-351.
  • [54]Hui JS, Wilson RS, Bennett DA, Bienias JL, Gilley DW, Evans DA: Rate of cognitive decline and mortality in Alzheimer's disease. Neurology 2003, 61:1356-1361.
  • [55]Caracciolo B, Palmer K, Monastero R, Winblad B, Backman L, Fratiglioni L: Occurrence of cognitive impairment and dementia in the community: a 9-year-long prospective study. Neurology 2008, 70:1778-1785.
  • [56]Chakravarti S, Collins WP, Forecast JD, Newton JR, Oram DH, Studd JW: Hormonal profiles after the menopause. Br Med J 1976, 2:784-787.
  • [57]Veldhuis JD: Aging and hormones of the hypothalamo-pituitary axis: gonadotropic axis in men and somatotropic axes in men and women. Ageing Res Rev 2008, 7:189-208.
  • [58]Ferrini RL, Barrett-Connor E: Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 1998, 147:750-754.
  • [59]Merry BJ, Holehan AM: Aging of the Female Reproductive System: The Menopause. In Physiological Basis of Aging and Geriatrics. 2nd edition. Edited by Timiras PS. CRC Press, Inc, Boca Raton; 1994:147-170.
  • [60]Morley JE, Kaiser F, Raum WJ, Perry HM 3rd, Flood JF, Jensen J, Silver AJ, Roberts E: 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 U S A 1997, 94:7537-7542.
  • [61]Nelson JF, Latham KR, Finch CE: Plasma testosterone levels in C57BL/6J male mice: effects of age and disease. Acta Endocrinol (Copenh) 1975, 80:744-752.
  • [62]Nelson JF, Felicio LS, Osterburg HH, Finch CE: Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of C57BL/6J mice. Endocrinology 1992, 130:805-810.
  • [63]Finch CE, Jonec V, Wisner JR Jr, Sinha YN, de Vellis JS, Swerdloff RS: Hormone production by the pituitary and testes of male C57BL/6J mice during aging. Endocrinology 1977, 101:1310-1317.
  • [64]Eleftheriou BE, Lucas LA: Age-related changes in testes, seminal vesicles and plasma testosterone levels in male mice. Gerontologia 1974, 20:231-238.
  • [65]Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, et al.: 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 2003, 289:2651-2662.
  • [66]Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick ML, Hendrix SL, Lewis CE, et al.: Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004, 291:2947-2958.
  • [67]Grady D, Yaffe K, Kristof M, Lin F, Richards C, Barrett-Connor E: Effect of postmenopausal hormone therapy on cognitive function: the heart and estrogen/progestin replacement study. Am J Med 2002, 113:543-548.
  • [68]Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, et al.: Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study. JAMA 2000, 283:1007-1015.
  • [69]Henderson VW, Paganini-Hill A, Miller BL, Elble RJ, Reyes PF, Shoupe D, McCleary CA, Klein RA, Hake AM, Farlow MR: Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial. Neurology 2000, 54:295-301.
  • [70]Wang PN, Liao SQ, Liu RS, Liu CY, Chao HT, Lu SR, Yu HY, Wang SJ, Liu HC: Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology 2000, 54:2061-2066.
  • [71]Wise PM, Suzuki S, Brown CM: Estradiol: a hormone with diverse and contradictory neuroprotective actions. Dialogues Clin Neurosci 2009, 11:297-303.
  • [72]Turgeon JL, McDonnell DP, Martin KA, Wise PM: Hormone therapy: physiological complexity belies therapeutic simplicity. Science 2004, 304:1269-1273.
  • [73]Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Miller VM, Naftolin F, Santoro N: KEEPS: the Kronos Early Estrogen Prevention Study. Climacteric 2005, 8:3-12.
  • [74]Golde TE, Schneider LS, Koo EH: Anti-abeta therapeutics in Alzheimer's disease: the need for a paradigm shift. Neuron 2011, 69:203-213.
  • [75]Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ: Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010, 9:119-128.
  • [76]Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB: 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 Metabol 2002, 87:589-598.
  • [77]Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR: Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metabol 2001, 86:724-731.
  • [78]Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Morley PM, Stauber PM, Vellas B, Baumgartner RN, Garry PJ: Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism: clinical and experimental 1997, 46:410-413.
  • [79]Liu PY, Beilin J, Meier C, Nguyen TV, Center JR, Leedman PJ, Seibel MJ, Eisman JA, Handelsman DJ: Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. J Clin Endocrinol Metabol 2007, 92:3599-3603.
  • [80]Hammond GL: Access of reproductive steroids to target tissues. Obstet Gynecol Clin North Am 2002, 29:411-423.
  • [81]Hammond GL: Diverse roles for sex hormone-binding globulin in reproduction. Biol Reprod 2011, 85:431-441.
  • [82]Muller M, Schupf N, Manly JJ, Mayeux R, Luchsinger JA: Sex hormone binding globulin and incident Alzheimer's disease in elderly men and women. Neurobiol Aging 2010, 31:1758-1765.
  • [83]Hoskin EK, Tang MX, Manly JJ, Mayeux R: Elevated sex-hormone binding globulin in elderly women with Alzheimer's disease. Neurobiol Aging 2004, 25:141-147.
  • [84]Paoletti AM, Congia S, Lello S, Tedde D, Orru M, Pistis M, Pilloni M, Zedda P, Loddo A, Melis GB: Low androgenization index in elderly women and elderly men with Alzheimer's disease. Neurology 2004, 62:301-303.
  • [85]Rosario ER, Pike CJ: Androgen regulation of beta-amyloid protein and the risk of Alzheimer's disease. Brain Res Rev 2008, 57:444-453.
  • [86]Fitzgerald C, Zimon AE, Jones EE: Aging and reproductive potential in women. Yale J Biol Med 1998, 71:367-381.
  • [87]Downs JL, Wise PM: The role of the brain in female reproductive aging. Mol Cell Endocrinol 2009, 299:32-38.
  • [88]Kermath BA, Gore AC: Neuroendocrine control of the transition to reproductive senescence: lessons learned from the female rodent model. Neuroendocrinology 2012, 96:1-12.
  • [89]Mobbs CV, Gee DM, Finch CE: Reproductive senescence in female C57BL/6J mice: ovarian impairments and neuroendocrine impairments that are partially reversible and delayable by ovariectomy. Endocrinology 1984, 115:1653-1662.
  • [90]Mayer LP, Devine PJ, Dyer CA, Hoyer PB: The follicle-deplete mouse ovary produces androgen. Biol Reprod 2004, 71:130-138.
  • [91]Arnold AP, Chen X: What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues? Front Neuroendocrinol 2009, 30:1-9.
  • [92]McCarthy MM, Arnold AP, Ball GF, Blaustein JD, De Vries GJ: Sex differences in the brain: the not so inconvenient truth. J Neurosci 2012, 32:2241-2247.
  • [93]Baker HW, Burger HG, de Kretser DM, Hudson B, O'Connor S, Wang C, Mirovics A, Court J, Dunlop M, Rennie GC: Changes in the pituitary-testicular system with age. Clin Endocrinol (Oxf) 1976, 5:349-372.
  • [94]Hale GE, Burger HG: Hormonal changes and biomarkers in late reproductive age, menopausal transition and menopause. Best Pract Res Clin Obstet Gynaecol 2009, 23:7-23.
  • [95]Ostergard DR, Parlow AF, Townsend DE: Acute effect of castration on serum FSH and LH in the adult woman. J Clin Endocrinol Metabol 1970, 31:43-47.
  • [96]Monroe SE, Jaffee RB, Midgley AJ: Regulation of human gonadotropins: 13. Changes in serum gonadotropins in menstruating women in response to oophorectomy. J Clin Endocrinol 1972, 34:420-422.
  • [97]Naik SI, Young LS, Charlton HM, Clayton RN: Pituitary gonadotropin-releasing hormone receptor regulation in mice. II: Females. Endocrinology 1984, 115:114-120.
  • [98]Naik SI, Young LS, Charlton HM, Clayton RN: Pituitary gonadotropin-releasing hormone receptor regulation in mice. I: Males. Endocrinology 1984, 115:106-113.
  • [99]Danilovich N, Babu PS, Xing W, Gerdes M, Krishnamurthy H, Sairam MR: Estrogen deficiency, obesity, and skeletal abnormalities in follicle-stimulating hormone receptor knockout (FORKO) female mice. Endocrinology 2000, 141:4295-4308.
  • [100]Danilovich N, Maysinger D, Sairam MR: Perspectives on reproductive senescence and biological aging: studies in genetically altered follitropin receptor knockout [FORKO] mice. Exp Gerontol 2004, 39:1669-1678.
  • [101]Jucker M: The benefits and limitations of animal models for translational research in neurodegenerative diseases. Nat Med 2010, 16:1210-1214.
  • [102]Ashe KH, Zahs KR: Probing the biology of Alzheimer's disease in mice. Neuron 2010, 66:631-645.
  • [103]Roberson ED: Contemporary approaches to Alzheimer's disease and frontotemporal dementia. Methods Mol Biol 2011, 670:1-9.
  • [104]Hoe HS, Lee HK, Pak DT: The upside of APP at synapses. CNS Neurosci Ther 2012, 18:47-56.
  • [105]Lazarov O, Demars MP: All in the Family: how the APPs Regulate Neurogenesis. Front Neurosci 2012, 6:81.
  • [106]Reaume AG, Howland DS, Trusko SP, Savage MJ, Lang DM, Greenberg BD, Siman R, Scott RW: Enhanced amyloidogenic processing of the beta-amyloid precursor protein in gene-targeted mice bearing the Swedish familial Alzheimer's disease mutations and a "humanized" Abeta sequence. J Biol Chem 1996, 271:23380-23388.
  • [107]Flood DG, Reaume AG, Dorfman KS, Lin YG, Lang DM, Trusko SP, Savage MJ, Annaert WG, De Strooper B, Siman R, Scott RW: FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction. Neurobiol Aging 2002, 23:335-348.
  • [108]Malthankar-Phatak GH, Lin YG, Giovannone N, Siman R: Amyloid deposition and advanced age fails to induce Alzheimer's type progression in a double knock-in mouse model. Aging dis 2012, 3:141-155.
  • [109]Morris RG: Episodic-like memory in animals: psychological criteria, neural mechanisms and the value of episodic-like tasks to investigate animal models of neurodegenerative disease. Philos Trans R Soc Lond B Biol Sci 2001, 356:1453-1465.
  • [110]Maguire JL, Stell BM, Rafizadeh M, Mody I: Ovarian cycle-linked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat Neurosci 2005, 8:797-804.
  • [111]Fata JE, Chaudhary V, Khokha R: Cellular turnover in the mammary gland is correlated with systemic levels of progesterone and not 17beta-estradiol during the estrous cycle. Biol Reprod 2001, 65:680-688.
  • [112]Walmer DK, Wrona MA, Hughes CL, Nelson KG: Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone. Endocrinology 1992, 131:1458-1466.
  • [113]Wood GA, Fata JE, Watson KL, Khokha R: Circulating hormones and estrous stage predict cellular and stromal remodeling in murine uterus. Reproduction 2007, 133:1035-1044.
  • [114]Melnikova T, Savonenko A, Wang Q, Liang X, Hand T, Wu L, Kaufmann WE, Vehmas A, Andreasson KI: Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern. Neuroscience 2006, 141:1149-1162.
  • [115]Clinton LK, Billings LM, Green KN, Caccamo A, Ngo J, Oddo S, McGaugh JL, LaFerla FM: Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis 2007, 28:76-82.
  • [116]Carroll JC, Rosario ER, Kreimer S, Villamagna A, Gentzschein E, Stanczyk FZ, Pike CJ: Sex differences in beta-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure. Brain Res 2010, 1366:233-245.
  • [117]Pietropaolo S, Sun Y, Li R, Brana C, Feldon J, Yee BK: The impact of voluntary exercise on mental health in rodents: a neuroplasticity perspective. Behav Brain Res 2008, 192:42-60.
  • [118]Gimenez-Llort L, Garcia Y, Buccieri K, Revilla S, Sunol C, Cristofol R, Sanfeliu C: Gender-specific neuroimmunoendocrine response to treadmill exercise in 3xTg-AD Mice. Int J Alzheimers Dis 2010, 2010:128354.
  • [119]King DL, Arendash GW, Crawford F, Sterk T, Menendez J, Mullan MJ: Progressive and gender-dependent cognitive impairment in the APP(SW) transgenic mouse model for Alzheimer's disease. Behav Brain Res 1999, 103:145-162.
  • [120]Gimenez-Llort L, Arranz L, Mate I, De la Fuente M: Gender-specific neuroimmunoendocrine aging in a triple-transgenic 3xTg-AD mouse model for Alzheimer's disease and its relation with longevity. Neuroimmunomodulation 2008, 15:331-343.
  • [121]Howlett DR, Richardson JC, Austin A, Parsons AA, Bate ST, Davies DC, Gonzalez MI: Cognitive correlates of Abeta deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes. Brain Res 2004, 1017:130-136.
  • [122]O'Leary TP, Brown RE: Visuo-spatial learning and memory deficits on the Barnes maze in the 16-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease. Behav Brain Res 2009, 201:120-127.
  • [123]Hirata-Fukae C, Li HF, Hoe HS, Gray AJ, Minami SS, Hamada K, Niikura T, Hua F, Tsukagoshi-Nagai H, Horikoshi-Sakuraba Y, et al.: Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res 2008, 1216:92-103.
  • [124]Callahan MJ, Lipinski WJ, Bian F, Durham RA, Pack A, Walker LC: Augmented senile plaque load in aged female beta-amyloid precursor protein-transgenic mice. Am J Pathol 2001, 158:1173-1177.
  • [125]Schafer S, Wirths O, Multhaup G, Bayer TA: Gender dependent APP processing in a transgenic mouse model of Alzheimer's disease. J Neural Transm 2007, 114:387-394.
  • [126]Wang J, Tanila H, Puolivali J, Kadish I, van Groen T: Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice. Neurobiol Dis 2003, 14:318-327.
  • [127]Pistell PJ, Zhu M, Ingram DK: Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease. Neuroscience 2008, 152:594-600.
  • [128]Perez SE, Berg BM, Moore KA, He B, Counts SE, Fritz JJ, Hu YS, Lazarov O, Lah JJ, Mufson EJ: DHA diet reduces AD pathology in young APPswe/PS1 Delta E9 transgenic mice: possible gender effects. J Neurosci Res 2010, 88:1026-1040.
  • [129]Lin J, Li X, Yuan F, Lin L, Cook CL, Rao CV, Lei Z: Genetic ablation of luteinizing hormone receptor improves the amyloid pathology in a mouse model of Alzheimer disease. J Neuropathol Exp Neurol 2010, 69:253-261.
  • [130]Schuessel K, Schafer S, Bayer TA, Czech C, Pradier L, Muller-Spahn F, Muller WE, Eckert A: Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiol Dis 2005, 18:89-99.
  • [131]Minami SS, Sidahmed E, Aid S, Shimoji M, Niikura T, Mocchetti I, Rebeck GW, Prendergast JS, Dealwis C, Wetzel R, et al.: Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Abeta/amyloid burden in a transgenic mouse model of Alzheimer's disease. J Neuroinflammation 2010, 7:57. BioMed Central Full Text
  • [132]Oliveira SM, Ribeiro CA, Cardoso I, Saraiva MJ: Gender-dependent transthyretin modulation of brain amyloid-beta levels: evidence from a mouse model of Alzheimer's disease. J Alzheimers Dis 2011, 27:429-439.
  • [133]Pacheco-Quinto J, de Turco EB R, DeRosa S, Howard A, Cruz-Sanchez F, Sambamurti K, Refolo L, Petanceska S, Pappolla MA: Hyperhomocysteinemic Alzheimer's mouse model of amyloidosis shows increased brain amyloid beta peptide levels. Neurobiol Dis 2006, 22:651-656.
  • [134]Park IH, Hwang EM, Hong HS, Boo JH, Oh SS, Lee J, Jung MW, Bang OY, Kim SU, Mook-Jung I: Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice. Neurobiol Aging 2003, 24:637-643.
  • [135]Touma C, Ambree O, Gortz N, Keyvani K, Lewejohann L, Palme R, Paulus W, Schwarze-Eicker K, Sachser N: Age- and sex-dependent development of adrenocortical hyperactivity in a transgenic mouse model of Alzheimer's disease. Neurobiol Aging 2004, 25:893-904.
  • [136]Overk CR, Lu PY, Wang YT, Choi J, Shaw JW, Thatcher GR, Mufson EJ: Effects of aromatase inhibition versus gonadectomy on hippocampal complex amyloid pathology in triple transgenic mice. Neurobiol Dis 2012, 45:479-487.
  • [137]Devi L, Alldred MJ, Ginsberg SD, Ohno M: Sex- and brain region-specific acceleration of beta-amyloidogenesis following behavioral stress in a mouse model of Alzheimer's disease. Mol Brain 2010, 3:34. BioMed Central Full Text
  • [138]Lee JY, Cole TB, Palmiter RD, Suh SW, Koh JY: Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc Natl Acad Sci U S A 2002, 99:7705-7710.
  • [139]Oikawa N, Ogino K, Masumoto T, Yamaguchi H, Yanagisawa K: Gender effect on the accumulation of hyperphosphorylated tau in the brain of locus-ceruleus-injured APP-transgenic mouse. Neurosci Lett 2010, 468:243-247.
  • [140]Maynard CJ, Cappai R, Volitakis I, Cherny RA, Masters CL, Li QX, Bush AI: Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology. J Inorg Biochem 2006, 100:952-962.
  • [141]Nakashima AS, Oddo S, Laferla FM, Dyck RH: Experience-dependent regulation of vesicular zinc in male and female 3xTg-AD mice. Neurobiol Aging 2010, 31:605-613.
  • [142]Barrier L, Ingrand S, Fauconneau B, Page G: Gender-dependent accumulation of ceramides in the cerebral cortex of the APP(SL)/PS1Ki mouse model of Alzheimer's disease. Neurobiol Aging 2010, 31:1843-1853.
  • [143]Ash ES, Alavijeh MS, Palmer AM, Mitchelmore C, Howlett DR, Francis PT, Broadstock M, Richardson JC: Neurochemical changes in a double transgenic mouse model of Alzheimer's disease fed a pro-oxidant diet. Neurochem Int 2010, 57:504-511.
  • [144]Hsiao KK, Borchelt DR, Olson K, Johannsdottir R, Kitt C, Yunis W, Xu S, Eckman C, Younkin S, Price D, et al.: Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 1995, 15:1203-1218.
  • [145]Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, et al.: Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 2007, 55:697-711.
  • [146]Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L: Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 2007, 316:750-754.
  • [147]Roberson ED, Halabisky B, Yoo JW, Yao J, Chin J, Yan F, Wu T, Hamto P, Devidze N, Yu GQ, et al.: Amyloid-beta/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. J Neurosci 2011, 31:700-711.
  • [148]Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fulop L, Penke B, Zilberter Y, Harkany T, Pitkanen A, Tanila H: Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 2009, 29:3453-3462.
  • [149]Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wolfing H, Chieng BC, Christie MJ, Napier IA, et al.: Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 2010, 142:387-397.
  • [150]Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, et al.: Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 2012, 149:708-721.
  • [151]Woolley CS: Acute effects of estrogen on neuronal physiology. Annu Rev Pharmacol Toxicol 2007, 47:657-680.
  • [152]Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS: Uncovering the mechanisms of estrogen effects on hippocampal function. Front Neuroendocrinol 2008, 29:219-237.
  • [153]Foy MR, Baudry M, Diaz Brinton R, Thompson RF: Estrogen and hippocampal plasticity in rodent models. J Alzheimers Dis 2008, 15:589-603.
  • [154]Brinton RD, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J: Progesterone receptors: form and function in brain. Front Neuroendocrinol 2008, 29:313-339.
  • [155]Holland J, Bandelow S, Hogervorst E: Testosterone levels and cognition in elderly men: a review. Maturitas 2011, 69:322-337.
  • [156]Pike CJ, Nguyen TV, Ramsden M, Yao M, Murphy MP, Rosario ER: Androgen cell signaling pathways involved in neuroprotective actions. Horm Behav 2008, 53:693-705.
  • [157]Frye CA: Neurosteroids' effects and mechanisms for social, cognitive, emotional, and physical functions. Psychoneuroendocrinology 2009, 34(Suppl 1):S143-161.
  • [158]Wang JM, Liu L, Irwin RW, Chen S, Brinton RD: Regenerative potential of allopregnanolone. Brain Res Rev 2008, 57:398-409.
  • [159]Heikkinen T, Kalesnykas G, Rissanen A, Tapiola T, Iivonen S, Wang J, Chaudhuri J, Tanila H, Miettinen R, Puolivali J: Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation. Exp Neurol 2004, 187:105-117.
  • [160]Golub MS, Germann SL, Mercer M, Gordon MN, Morgan DG, Mayer LP, Hoyer PB: Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe mouse. Neurobiol Aging 2008, 29:1512-1523.
  • [161]Levin-Allerhand JA, Lominska CE, Wang J, Smith JD: 17Alpha-estradiol and 17beta-estradiol treatments are effective in lowering cerebral amyloid-beta levels in AbetaPPSWE transgenic mice. J Alzheimers Dis 2002, 4:449-457.
  • [162]Carroll JC, Pike CJ: Selective estrogen receptor modulators differentially regulate Alzheimer-like changes in female 3xTg-AD mice. Endocrinology 2008, 149:2607-2611.
  • [163]Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, LaFerla FM, Pike CJ: Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci 2007, 27:13357-13365.
  • [164]Carroll JC, Rosario ER, Villamagna A, Pike CJ: Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3xTransgenic-Alzheimer's disease mice. Endocrinology 2010, 151:2713-2722.
  • [165]Zhao L, Yao J, Mao Z, Chen S, Wang Y, Brinton RD: 17beta-Estradiol regulates insulin-degrading enzyme expression via an ERbeta/PI3-K pathway in hippocampus: relevance to Alzheimer's prevention. Neurobiol Aging 2011, 32:1949-1963.
  • [166]Xu H, Wang R, Zhang YW, Zhang X: Estrogen, beta-amyloid metabolism/trafficking, and Alzheimer's disease. Ann N Y Acad Sci 2006, 1089:324-342.
  • [167]Zheng H, Xu H, Uljon SN, Gross R, Hardy K, Gaynor J, Lafrancois J, Simpkins J, Refolo LM, Petanceska S, et al.: Modulation of A(beta) peptides by estrogen in mouse models. J Neurochem 2002, 80:191-196.
  • [168]Amtul Z, Wang L, Westaway D, Rozmahel RF: Neuroprotective mechanism conferred by 17beta-estradiol on the biochemical basis of Alzheimer's disease. Neuroscience 2010, 169:781-786.
  • [169]Frye CA, Walf AA: Effects of progesterone administration and APPswe+PSEN1Deltae9 mutation for cognitive performance of mid-aged mice. Neurobiol Learn Mem 2008, 89:17-26.
  • [170]Green PS, Bales K, Paul S, Bu G: Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease. Endocrinology 2005, 146:2774-2781.
  • [171]Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, Harada N, Zhong Z, Shen Y, Li R: Brain estrogen deficiency accelerates Abeta plaque formation in an Alzheimer's disease animal model. Proc Natl Acad Sci U S A 2005, 102:19198-19203.
  • [172]Levin-Allerhand JA, Smith JD: Ovariectomy of young mutant amyloid precursor protein transgenic mice leads to increased mortality. J Mol Neurosci 2002, 19:163-166.
  • [173]Hogervorst E, Williams J, Budge M, Barnetson L, Combrinck M, Smith AD: Serum total testosterone is lower in men with Alzheimer's disease. Neuro Endocrinol Lett 2001, 22:163-168.
  • [174]Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM: Free testosterone and risk for Alzheimer disease in older men. Neurology 2004, 62:188-193.
  • [175]Rosario ER, Chang L, Stanczyk FZ, Pike CJ: Age-related testosterone depletion and the development of Alzheimer disease. JAMA 2004, 292:1431-1432.
  • [176]Moffat SD: Does testosterone mediate cognitive decline in elderly men? J Gerontol A Biol Sci Med Sci 2006, 61:521.
  • [177]Rosario ER, Carroll JC, Oddo S, LaFerla FM, Pike CJ: Androgens regulate the development of neuropathology in a triple transgenic mouse model of Alzheimer's disease. J Neurosci 2006, 26:13384-13389.
  • [178]McAllister C, Long J, Bowers A, Walker A, Cao P, Honda S, Harada N, Staufenbiel M, Shen Y, Li R: Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment. J Neurosci 2010, 30:7326-7334.
  • [179]Rosario ER, Carroll J, Pike CJ: Testosterone regulation of Alzheimer-like neuropathology in male 3xTg-AD mice involves both estrogen and androgen pathways. Brain Res 2010, 1359:281-290.
  • [180]Casadesus G, Webber KM, Atwood CS, Pappolla MA, Perry G, Bowen RL, Smith MA: Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice. Biochim Biophys Acta 2006, 1762:447-452.
  文献评价指标  
  下载次数:39次 浏览次数:23次