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Testing Direct Effects of Soy Daidzein on Fragile X Phenotypes

测试大豆黄酮对脆性 X 表型的直接影响

基本信息

批准号：
8701184
负责人：
CARA JEAN WESTMARK
金额：
$ 7.31万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-15 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8701184
关键词：
Adult Anxiety Applications Grants Attenuated Autistic Disorder Behavioral Biological Factors Biological Markers Biological Models Body Weight Chemicals Clinical Data Collection Consumption Data Development Diagnosis Diet Dietary Intervention Dose Drug Kinetics Exhibits Foundations Fragile X Syndrome Goals Health Benefit Hormones Human Characteristics Hyperactive behavior Impaired cognition Incidence Infant Infant formula Inherited Intake Intellectual functioning disability Laboratories Maintenance Medical Records Metabolism Molecular Mus Nervous System Trauma Neurodevelopmental Disorder Neurologic Outcome Patients Phenotype Physiologic pulse Phytoestrogens Pilot Projects Plants Predisposition Pregnancy Property Research Rodent Rodent Model Seizures Sensory Solid Soy Proteins Supplementation Testing Therapeutic Therapeutic Intervention Time Transgenic Mice audiogenic seizure autistic children base critical period daidzein dietary supplements early childhood feeding fetal infancy mouse model open field behavior postnatal pre-clinical prepulse inhibition prevent public health relevance research study response soy

项目摘要

DESCRIPTION (provided by applicant): This project explores the untested hypothesis that the soy phytoestrogen daidzein exacerbates fragile X syndrome (FXS) phenotypes. FXS is the most common form of inherited intellectual disability. Serendipitous findings from our laboratory indicate that a soy-based diet increases seizure incidence in a mouse model of FXS, Fmr1KO mice, as well as in infants later diagnosed with autism. In the mouse studies, a seizure-promoting ingredient in the soy was identified as the soy phytoestrogen daidzein. We hypothesize that a soy-based diet during postnatal development exacerbates multiple FXS phenotypes. This grant application is a pilot study to determine the pharmacokinetics of daidzein and its metabolites in WT and Fmr1KO mice as well as their effects on well-established FXS phenotypes including seizure threshold, anxiety, hyperactivity and sensorimotor gating. Successful experimental outcomes will provide the preliminary data for an RO1 grant application to test the rescue of additional FXS phenotypes in Fmr1KO mice in response to a soy-free diet as well as the underlying molecular mechanism. The long-term goal of this project is provide solid pre-clinical data in Fmr1KO mice that support the restriction of soy-based infant formulas for babies with FXS and other neurodevelopmental disorders.

描述（由申请人提供）：该项目探讨了大豆植物雌激素大豆苷元加剧脆性X综合征（FXS）表型的未经检验的假设。FXS是遗传性智力残疾最常见的形式。我们实验室的偶然发现表明，以大豆为基础的饮食增加了FXS小鼠模型，Fmr1KO小鼠以及后来诊断为自闭症的婴儿的癫痫发作率。在老鼠的研究中，大豆中的一种促进衰老的成分被确定为大豆植物雌激素大豆黄酮。我们推测，在出生后发育期间，以大豆为基础的饮食会加剧多种FXS表型。这项拨款申请是一项试点研究，以确定大豆苷元及其代谢产物在WT和Fmr1KO小鼠中的药代动力学，以及它们对成熟的FXS表型的影响，包括癫痫发作阈值，焦虑，多动和感觉运动门控。成功的实验结果将为RO1资助申请提供初步数据，以测试在无大豆饮食以及潜在的分子机制下，对Fmr1KO小鼠中其他FXS表型的拯救。该项目的长期目标是在Fmr1KO小鼠中提供可靠的临床前数据，支持限制FXS和其他神经发育障碍婴儿使用大豆婴儿配方奶粉。