Memory Impairment in Estrogen Receptor α Knockout Mice Through Accumulation of Amyloid-β Peptides

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• 作者：Chul Ju Hwang ; Hyung-Mun Yun ; Kyung-Ran Park ; Ju Kyung Song…
• 关键词：Alzheimer’s disease ; Amyloid ; Estrogens ; Estrogen receptor alpha ; Neprilysin ; Neurogenic inflammation
• 刊名：Molecular Neurobiology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：52
• 期：1
• 页码：176-186
• 全文大小：8,484 KB
• 参考文献：1.Shughrue PJ, Lane MV, Merchenthaler I (1997) Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J Comp Neurol 388(4):507-25PubMed View Article
  2.Janicki SC, Schupf N (2010) Hormonal influences on cognition and risk for Alzheimer’s disease. Curr Neurol Neurosci Reports 10(5):359-66. doi:10.-007/?s11910-010-0122-6 View Article
  3.Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, Aggerwal A, David Curb J, Hendrix SL, Allan Hubbell F, Khandekar J, Lane DS, Lasser N, Lopez AM, Potter J, Ritenbaugh C (2006) Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestin. Maturitas 55(2):103-15. doi:10.-016/?j.?maturitas.-006.-5.-04 PubMed View Article
  4.Espeland MA, Hogan PE, Fineberg SE, Howard G, Schrott H, Waclawiw MA, Bush TL (1998) Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Diabetes care 21(10):1589-595PubMed View Article
  5.Henderson VW (2010) Action of estrogens in the aging brain: dementia and cognitive aging. Biochim Biophys Acta 1800(10):1077-083. doi:10.-016/?j.?bbagen.-009.-1.-05 PubMed View Article
  6.Levin-Allerhand J, McEwen BS, Lominska CE, Lubahn DB, Korach KS, Smith JD (2001) Brain region-specific up-regulation of mouse apolipoprotein E by pharmacological estrogen treatments. J Neurochem 79(4):796-03PubMed View Article
  7.Xu H, Gouras GK, Greenfield JP, Vincent B, Naslund J, Mazzarelli L, Fried G, Jovanovic JN, Seeger M, Relkin NR, Liao F, Checler F, Buxbaum JD, Chait BT, Thinakaran G, Sisodia SS, Wang R, Greengard P, Gandy S (1998) Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nat Med 4(4):447-51PubMed View Article
  8.Wang DS, Dickson DW, Malter JS (2006) beta-Amyloid degradation and Alzheimer’s disease. J Biomed Biotechnol 3:58406. doi:10.-155/?JBB/-006/-8406
  9.Yasojima K, Akiyama H, McGeer EG, McGeer PL (2001) Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of beta-amyloid peptide. Neurosci Lett 297(2):97-00PubMed View Article
  10.Hellstrom-Lindahl E, Ravid R, Nordberg A (2008) Age-dependent decline of neprilysin in Alzheimer’s disease and normal brain: inverse correlation with A beta levels. Neurobiol Aging 29(2):210-21. doi:10.-016/?j.?neurobiolaging.-006.-0.-10 PubMed View Article
  11.Huang J, Guan H, Booze RM, Eckman CB, Hersh LB (2004) Estrogen regulates neprilysin activity in rat brain. Neurosci Lett 367(1):85-7. doi:10.-016/?j.?neulet.-004.-5.-85 PubMed View Article
  12.Foster TC (2012) Role of estrogen receptor alpha and beta expression and signaling on cognitive function during aging. Hippocampus 22(4):656-69. doi:10.-002/?hipo.-0935 PubMed Central PubMed View Article
  13.Nabeshima T, Nitta A (1994) Memory impairment and neuronal dysfunction induced by beta-amyloid protein in rats. Tohoku J Exp Med 174(3):241-49PubMed View Article
  14.Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11(1):47-0PubMed View Article
  15.Limon D, Diaz A, Hernandez M, Fernandez GJ, Torres-Martinez AC, Perez-Severiano F, Rendon-Huerta EP, Montano LF, Guevara J (2012) Neuroprotective effect of the aminoestrogen prolame against impairment of learning and memory skills in rats injected with amyloid-beta-25-5 into the hippocampus. Eur J Pharmacol 685(1-):74-0. doi:10.-016/?j.?ejphar.-012.-4.-20 PubMed View Article
  16.Xu WJ, Xu F, Anderson ME, Kotarba AE, Davis J, Robinson JK, Van Nostrand WE (2013) Cerebral microvascular rather than parenchymal amyloid-beta protein pathology promotes early cognitive impairment in transgenic mice. J Alzheimers Dis: JAD. doi:10.-233/?JAD-130758 PubMed Central
  17.Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353-56. doi:10.-126/?science.-072994 PubMed View Article
  18.Rune GM, Wehrenberg U, Prange-Kiel J, Zhou L, Adelmann G, Frotscher M (2002) Estrogen up-regulates estrogen receptor alpha and synaptophysin in slice cultures of rat hippocampus. Neuroscience 113(1):167-75PubMed View Article
  19.Nishida Y, Ito S, Ohtsuki S, Yamamoto N, Takahashi T, Iwata N, Jishage K, Yamada H, Sasaguri H, Yokota S, Piao W, Tomimitsu H, Saido TC, Yanagisawa K, Terasaki T, Mizusawa H, Yokota T (2009) Depletion of vitamin E increases amyloid beta accumulation by decreasing its clearances from brain and blood in a mouse model of Alzheimer disease. J Biol Chem 284(48):33400-3408. doi:10.-074/?jbc.?M109.-54056 PubMed Central PubMed View Article
  20.Li R, He P, Cui J, Staufenbiel M, Harada N, Shen Y (2013) Brain endogenous estrogen levels determine responses to estrogen replacement therapy via regulation of
• 作者单位：Chul Ju Hwang (1)
  Hyung-Mun Yun (1)
  Kyung-Ran Park (1)
  Ju Kyung Song (1)
  Hyun Ok Seo (1)
  Byung Kook Hyun (1)
  Dong Young Choi (2)
  Hwan-Soo Yoo (1)
  Ki-Wan Oh (1)
  Dae Yeun Hwang (3)
  Sang-Bae Han (1)
  Jin Tae Hong (1) (4)
  
  1. College of Pharmacy and Medical Research Center, Chungbuk National University, 52, Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea
  2. College of Pharmacy, Young Nam University, Dae, Gyeongsan, Gyeongbuk, 712-749, Republic of Korea
  3. College of Natural Resources & Life Science, Pusan National University, Pusan, Republic of Korea
  4. College of Pharmacy, Medical Research Center, Chungbuk National University, 12, Gaeshin-dong, Heungdeok-gu, Cheongju, Chungbuk, 361-763, Republic of Korea
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

Estrogen has been known to reduce the development of Alzheimer’s disease (AD). However, exact mechanisms are not clear. We investigated whether estrogen can increase amyloid-beta (Aβ) degradation and affects Aβ-induced memory impairment in an estrogen deficiency model. Estrogen receptor alpha (ERα) knockout mice and wild-type mice were intracerebroventricular (ICV) infused with Aβ (300?pmol) for 2?weeks. Cognitive function was then assessed by the Morris water maze test and passive avoidance test. In addition, Western blot analysis, immunostaining, immunofluorescence staining, ELISA, and enzyme activity assays were used to examine the degree of Aβ deposition in the brains of ERα knockout mice. In our present study, Aβ was accumulated more in the ERα knockout mice brain and greatly worsened memory impairment and glial activation as well as neurogenic inflammation. These results suggest that estrogen may protect memory impairment by stimulating the degradation of Aβ and down-regulate neurogenic inflammation as well as amyloidogenesis.