Soy phytoestrogen neuroprotection in cerebral ischemia

大豆植物雌激素对脑缺血的神经保护作用

• 批准号: 7173879
• 负责人: DEREK A SCHREIHOFER
• 金额: $ 27.65万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7173879
• 关键词: Adverse effects; Apoptotic; Brain; Brain Injuries; Brain region; Brain-Derived Neurotrophic Factor; Cell Death; Cell Line; Cerebral Ischemia; Cerebrum; Clinical; Data; Diet; Dose; Estrogen Receptors; Estrogens; Female; Gene Activation; Genes; Genistein; Genomics; Health; Hormone replacement therapy; Hormones; Human; In Vitro; Incidence; Infarction; Ingestion; Malignant Neoplasms; Menopause; Middle Cerebral Artery Occlusion; Modeling; NGFR Protein; NGFR gene; Nerve Growth Factors; Neurodegenerative Disorders; Neurons; Numbers; Peripheral; Phytoestrogens; Plants; Rattus; Regulation; Replacement Therapy; Rodent Model; Selective Estrogen Receptor Modulators; Severities; Signal Pathway; Stroke; Testing; Traumatic Brain Injury; Woman; cancer risk; daidzein; equol; in vitro Model; in vivo; neuroprotection; non-genomic; size; soy

DESCRIPTION (provided by applicant): Estrogen is a powerful neuroprotective hormone that is particularly effective in reducing cerebral ischemic damage in stroke. Endogenous and exogenous estrogen is also associated with protection from neurodegenerative disease in humans. However, the benefits of estrogen are mitigated by recent clinical results suggesting that hormone replacement therapy (HRT) has health consequences. Concerns about hormone dependent cancer will continue to deter women from taking replacement therapy. Pharmacological selective estrogen receptor modulators (SERMs) show promise in preserving the beneficial effects of estrogen without increasing cancer risk. However, many women are already opting for "natural" SERMs such as plant derivatives containing soy and other phytoestrogens with the presumption that such therapies are both effective and safer than HRT. Epidemiological and experimental data suggest that diets high in soy phytoestrogens provide many of the same benefits as estrogen with the potential for decreased negative side effects seen with traditional HRT. Nevertheless, very little is known about the effects of dietary soy phytoestrogens in the brain. In vitro, soy phytoestrogens can mimic some of estrogen's neuroprotective actions, but these same compounds have also been shown to inhibit some estrogen actions in the brain. The present proposal seeks to determine the whether of soy phytoestrogens protect neurons from ischemic damage in vitro and in vivo. We hypothesize that physiologically relevant doses of soy phytoestrogens are neuroprotective by mimicking both genomic and non-genomic actions of estrogen. Aim 1 will test the hypothesis that the soy phytoestrogens genestein, daidzein, and equol inhibit apoptotic cell death in neuronal cell line models of cerebral ischemia in an estrogen receptor-dependent manner. Aim 2 will test the hypothesis that in the absence of endogenous estrogen a high soy diet will decrease infarct size and cell death associated with middle cerebral artery occlusion in rats. Aim 3 will test the hypothesis that in the absence of endogenous estrogen, ingestion of a high soy diet will induce the expression of the neuroprotective genes BDNF, NGF, Bcl-2, BCl-xL, and TrkB and reduce expression of the pro-apoptotic p75 NTR in brain regions damaged by middle cerebral artery occlusion. This proposal seeks to provide critical new information about the ability of phytoestrogens to protect the brain from focal cerebral ischemia.

描述（由申请人提供）：雌激素是一种强大的神经保护激素，对减少脑缺血损伤特别有效。内源性和外源性雌激素也与保护人类免受神经退行性疾病有关。然而，最近的临床结果表明激素替代疗法（HRT）对健康有影响，因此雌激素的益处被削弱了。对激素依赖性癌症的担忧将继续阻止女性接受替代疗法。选择性雌激素受体调节剂（SERMs）在保留雌激素的有益作用而不增加癌症风险方面显示出前景。然而，许多妇女已经开始选择“天然”的血清素，如含有大豆和其他植物雌激素的植物衍生物，她们认为这种疗法比激素替代疗法既有效又安全。流行病学和实验数据表明，富含大豆植物雌激素的饮食提供了许多与雌激素相同的益处，并且有可能减少传统激素替代疗法的负面副作用。然而，人们对膳食大豆植物雌激素对大脑的影响知之甚少。在体外实验中，大豆植物雌激素可以模仿雌激素的一些神经保护作用，但这些化合物也被证明可以抑制大脑中雌激素的一些作用。

项目成果

High-soy diet decreases infarct size after permanent middle cerebral artery occlusion in female rats.

高大豆饮食可减少雌性大鼠大脑中动脉永久性闭塞后的梗塞面积。

• DOI: 10.1152/ajpregu.00642.2004
• 发表时间: 2005
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Schreihofer,DerekA;Do,KhoiD;Schreihofer,AnnM
• 通讯作者: Schreihofer,AnnM

Effect of high soy diet on the cerebrovasculature and endothelial nitric oxide synthase in the ovariectomized rat.

• DOI: 10.1016/j.vph.2010.02.003
• 发表时间: 2010-05
• 期刊: VASCULAR PHARMACOLOGY
• 影响因子: 4
• 作者: Schreihofer, Derek A.;Deutsch, Christian;Lovekamp-Swan, Tara;Sullivan, Jennifer C.;Dorrance, Anne M.
• 通讯作者: Dorrance, Anne M.

Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats.

• DOI: 10.1016/j.neulet.2008.09.006
• 发表时间: 2008-11-14
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Glendenning ML;Lovekamp-Swan T;Schreihofer DA
• 通讯作者: Schreihofer DA

Soy phytoestrogens are neuroprotective against stroke-like injury in vitro.

• DOI: 10.1016/j.neuroscience.2008.10.003
• 发表时间: 2009-01-23
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Schreihofer DA;Redmond L
• 通讯作者: Redmond L