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Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2010 Apr 8;26(2):133–139. doi: 10.1007/s12264-010-0913-4

Effects of synaptic plasticity regulated by 17β-estradiol on learning and memory in rats with Alzheimer’s disease

雌二醇对阿尔茨海默病大鼠学习记忆能力及长时程增强的影响

Xiu-Li Shang 1, Jiu-Han Zhao 1, Yun-Peng Cao 1, Yi-Xue Xue 2,
PMCID: PMC5560370  PMID: 20332818

Abstract

Objective

To investigate whether estrogen modulates learning and memory and long-term potentiation (LTP) in the hippocampus of rats with Alzheimer’s disease (AD).

Methods

The rats were divided into ovariectomy (OVX) and estrogen replacement therapy (ERT) groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 μL (10 μg/μL) amyloid-beta peptide 1–40(Aβ1–40) into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively.

Results

The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group (P < 0.05). Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation (HFS), compared with that in OVX group (P < 0.01).

Conclusion

ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.

Keywords: estradiol, long-term potentiation, learning and memory, rat, Alzheimer’s disease

References

  • [1].Zandi P.P., Carlson M.C., Plasssman B.L., Welsh-Bohmer K.A., Mayer L.S., Steffens D.C., et al. Hormone replacement therapy and incidence of Alzheimer’s disease on older women: the Cache County study. JAMA. 2002;288(17):2123–2129. doi: 10.1001/jama.288.17.2123. [DOI] [PubMed] [Google Scholar]
  • [2].Dunkin J., Rasgon N., Wagner-Steh K., David S., Altshuler L., Rapkin A. Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women. Psychoneuroendocrinology. 2005;30(3):284–296. doi: 10.1016/j.psyneuen.2004.09.002. [DOI] [PubMed] [Google Scholar]
  • [3].Mulnard R.A., Cotman C.W., Kawas C., Van Dyck C.H., Sano M., Doody R., et al. Estrogen replacement therapy for treatment of mile to moderate Alzheimer disease: a randomized controlled trial. Alzheimer’s disease cooperative study. JAMA. 2000;283(8):1007–1015. doi: 10.1001/jama.283.8.1007. [DOI] [PubMed] [Google Scholar]
  • [4].Takuma K., Matsuo A., Himeno Y., Hoshina Y., Ohno Y., Funatsu Y., et al. 17beta-estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats. Neuroscience. 2007;146(1):60–68. doi: 10.1016/j.neuroscience.2007.01.017. [DOI] [PubMed] [Google Scholar]
  • [5].Green P.S., Bales K., Paul S., Bu G. Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer’s disease. Endocrinology. 2005;146(6):2774–2781. doi: 10.1210/en.2004-1433. [DOI] [PubMed] [Google Scholar]
  • [6].Shang X.L., Xu W.P., Liu Y.H., Yang J.X., Zhang H., Xue Y.X. Expression of MAPK in the hippocampus of Alzheimer’s disease rats model. Neurosci Bull. 2005;21(4):296–300. [Google Scholar]
  • [7].Nitta A., Itoh A., Hasegawa T., Nabeshima T. β-Amyloid proteininduced Alzheimer’s disease animal model. Neurosci Lett. 1994;170(1):63–66. doi: 10.1016/0304-3940(94)90239-9. [DOI] [PubMed] [Google Scholar]
  • [8].Wang M.N., Dong Z.F., Cao J., Xu L. Repeated morphine treatment influences operant and spatial learning differentially. Neurosci Bull. 2006;22(3):137–143. [PubMed] [Google Scholar]
  • [9].Heikkinen T., Kalesnykas G., Rissanen A., Tapiola T., Livonen S., Wang J., et al. Estrogen treatment improves spatial learning in APP + PS mice but does not affect beta amyloid accumulation and plaque formation. Exp Neurol. 2004;187(1):105–117. doi: 10.1016/j.expneurol.2004.01.015. [DOI] [PubMed] [Google Scholar]
  • [10].Sarkaki A., Amani R., Badavi M., Safahani M., Aligholi H. Effect of ovariectomy on reference memory version of Morris water maze in young adult rats. Iran Biomed J. 2008;12:123–128. [PubMed] [Google Scholar]
  • [11].For M.R., Baudry M., Diaz Brinton R., Moghddam A.Z., Aligholi H., Safahani M., et al. Estrogen and hippocampal plasticity in rodent models. Alzheimers Dis. 2008;15(8):589–603. doi: 10.3233/jad-2008-15406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Duff S.J., Hampson E. A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy. Horm Behav. 2000;38(4):262–276. doi: 10.1006/hbeh.2000.1625. [DOI] [PubMed] [Google Scholar]
  • [13].Sandstrom N.J., Williams C.L. Spatial memory retention is enhanced by acute and continuous estradiol replacement. Horm Behav. 2004;45(2):128–135. doi: 10.1016/j.yhbeh.2003.09.010. [DOI] [PubMed] [Google Scholar]
  • [14].Sandstrom N.J., Williams C.L. Memory retention is modulated by acute estradiol and progesterone replacement. Behav Neurosci. 2001;115(2):384–393. doi: 10.1037/0735-7044.115.2.384. [DOI] [PubMed] [Google Scholar]
  • [15].Carlson M.C., Zandi P.P., Plassman B.L., Tschanz J.T., Welsh-Bohmer K.A., Steffens D.C., et al. Hormone replacement therapy and reduced cognitive decline in older women: the Cache County study. Neurology. 2001;57(12):2210–2216. doi: 10.1212/wnl.57.12.2210. [DOI] [PubMed] [Google Scholar]
  • [16].Hogervorst E., Williams J., Budge M., Riedel W., Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis. Neuroscience. 2000;101(3):485–512. doi: 10.1016/S0306-4522(00)00410-3. [DOI] [PubMed] [Google Scholar]
  • [17].LeBlanc E.S., Janowsky J., Chan B.K., Nelson H.D. Hormone replacement therapy and cognition: systematic review and meta analysis. JAMA. 2001;285(23):1489–1499. doi: 10.1001/jama.285.11.1489. [DOI] [PubMed] [Google Scholar]
  • [18].Ancelin M.L., Ritchie K. Lifelong endocrine fluctuations and related cognitive disorders. Curr Pharm Des. 2005;11(32):4229–4252. doi: 10.2174/138161205774913228. [DOI] [PubMed] [Google Scholar]
  • [19].Rasgon N.L., Magunusson C., Johansson A.L., Pedersen N.L., Elman S., Gatz M. Endogenous and exogenous hormone exposure and risk of cognitive impairment in Swedish twins: a preliminary study. Psychoneuroendocrinology. 2005;30(6):558–567. doi: 10.1016/j.psyneuen.2005.01.004. [DOI] [PubMed] [Google Scholar]
  • [20].Kim J.S., Kim H.Y., Kim J.H., Shin H.K., Lee S.H., Lee Y.S., et al. Enhancement of rat hippocampal long-term potentioation by 17 beta-estradiol invoves mitogen-activated protein kinase-dependent and independent component. Neurosci Lett. 2002;332(1):65–69. doi: 10.1016/S0304-3940(02)00902-3. [DOI] [PubMed] [Google Scholar]
  • [21].Lee J.H., Lau K., Perkinton M.S., Standen C.L., Rogel B., Falinska A., et al. Neuronal adaptor protein X11beta reduces amyloid betaprotein levels and amyloid plaque formation in the brains of transgenic mice. J Biol Chem. 2004;279(47):49099–49104. doi: 10.1074/jbc.M405602200. [DOI] [PubMed] [Google Scholar]
  • [22].Zhang L., Xu J.Q., Rong S., Xie B.J., Sun Z.D., Zhang Y.J., et al. The mixture of procyanidins extracted from the lotus seed pool and bilobalide ameliorates scopolamine-induced memory impairment in mice. Neurosci Bull. 2009;25(4):203–208. doi: 10.1007/s12264-009-0309-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Ryan J., Scali J., Carriere I., Ritchie K., Ancelin M.L. Hormonal treatment mild cognitive impairment and Alzheimer’s disease. Int Psychogeriatr. 2008;20(1):47–56. doi: 10.1017/S1041610207006485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24].Shumaker S.A., Legault C., Rapp S.R., Thal L., Wallace R.B., Ockene J.K., et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study (WHIMS) JAMA. 2003;289(20):2651–2662. doi: 10.1001/jama.289.20.2651. [DOI] [PubMed] [Google Scholar]
  • [25].Shumaker S.A., Legault C., Kuller L., Rapp S.R., Thal L., Lane D.S., 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(24):2947–2958. doi: 10.1001/jama.291.24.2947. [DOI] [PubMed] [Google Scholar]
  • [26].Henderson V.W. Cognitive changes after menopause: influence of Estrogen. Clin Obstet Gynecol. 2008;51(3):618–626. doi: 10.1097/GRF.0b013e318180ba10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Resnick S.M., Henderson V.W. Hormone therapy and risk of Alzheimer disease: a critical time. JAMA. 2002;288(17):2170–2172. doi: 10.1001/jama.288.17.2170. [DOI] [PubMed] [Google Scholar]

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