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.
摘要
目的
探讨雌二醇对阿尔茨海默病(Alzheimer’s disease, AD)大鼠的学习记忆能力及长时程增强(long-term potentiation, LTP)的影响。
方法
大鼠随机分成卵巢切除 (ovariectomy, OVX)组和雌激素替代治疗(estrogen replace treatment, ERT)组。 两组大鼠均接受卵巢切除手术, ERT组大鼠随后接受雌激素替代治疗。 手术2周后, 两组大鼠海马内立体定位单侧注射1 μL Aβ1–40 (10 μg/μL), 建立AD模型。 运用水迷宫实验检测大鼠的学习和记忆能力, 并进行LTP记录和比较。
结果
OVX组AD大鼠的水迷宫逃避潜伏期相较于ERT组明显延长(P < 0.05)。 此外, 高频刺激(high frequence stimulation, HFS) 30 min后与HFS刺激前相比, ERT组LTP增加的幅值明显高于OVX组(P < 0.05)。
结论
雌激素替代治疗能改善AD大鼠的认知功能, 调整LTP及突触可塑性。
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References
Zandi PP, Carlson MC, Plasssman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, et al. Hormone replacement therapy and incidence of Alzheimer’s disease on older women: the Cache County study. JAMA 2002, 288(17): 2123–2129.
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.
Mulnard RA, Cotman CW, Kawas C, Van Dyck CH, 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.
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.
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(6): 2774–2781.
Shang XL, Xu WP, Liu YH, Yang JX, Zhang H, Xue YX. Expression of MAPK in the hippocampus of Alzheimer’s disease rats model. Neurosci Bull 2005, 21(4): 296–300.
Nitta A, Itoh A, Hasegawa T, Nabeshima T. β-Amyloid proteininduced Alzheimer’s disease animal model. Neurosci Lett 1994, 170(1): 63–66.
Wang MN, Dong ZF, Cao J, Xu L. Repeated morphine treatment influences operant and spatial learning differentially. Neurosci Bull 2006, 22(3): 137–143.
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.
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.
For MR, Baudry M, Diaz Brinton R, Moghddam AZ, Aligholi H, Safahani M, et al. Estrogen and hippocampal plasticity in rodent models. Alzheimers Dis 2008, 15(8): 589–603.
Duff SJ, Hampson E. A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy. Horm Behav 2000, 38(4): 262–276.
Sandstrom NJ, Williams CL. Spatial memory retention is enhanced by acute and continuous estradiol replacement. Horm Behav 2004, 45(2): 128–135.
Sandstrom NJ, Williams CL. Memory retention is modulated by acute estradiol and progesterone replacement. Behav Neurosci 2001, 115(2): 384–393.
Carlson MC, Zandi PP, Plassman BL, Tschanz JT, Welsh-Bohmer KA, Steffens DC, et al. Hormone replacement therapy and reduced cognitive decline in older women: the Cache County study. Neurology 2001, 57(12): 2210–2216.
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.
LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: systematic review and meta analysis. JAMA 2001, 285(23): 1489–1499.
Ancelin ML, Ritchie K. Lifelong endocrine fluctuations and related cognitive disorders. Curr Pharm Des 2005, 11(32): 4229–4252.
Rasgon NL, Magunusson C, Johansson AL, Pedersen NL, 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.
Kim JS, Kim HY, Kim JH, Shin HK, Lee SH, Lee YS, 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.
Lee JH, Lau Kf, Perkinton MS, Standen CL, 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.
Zhang L, Xu JQ, Rong S, Xie BJ, Sun ZD, Zhang YJ, 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.
Ryan J, Scali J, Carriere I, Ritchie K, Ancelin ML. Hormonal treatment mild cognitive impairment and Alzheimer’s disease. Int Psychogeriatr 2008, 20(1): 47–56.
Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, 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.
Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, 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.
Henderson VW. Cognitive changes after menopause: influence of Estrogen. Clin Obstet Gynecol 2008, 51(3): 618–626.
Resnick SM, Henderson VW. Hormone therapy and risk of Alzheimer disease: a critical time. JAMA 2002, 288(17): 2170–2172.
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Shang, XL., Zhao, JH., Cao, YP. et al. Effects of synaptic plasticity regulated by 17β-estradiol on learning and memory in rats with Alzheimer’s disease. Neurosci. Bull. 26, 133–139 (2010). https://doi.org/10.1007/s12264-010-0913-4
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DOI: https://doi.org/10.1007/s12264-010-0913-4