Mouse Model Neuro-Facial Dysmorphology: Tanslational and Treatment Studies

小鼠模型神经面部畸形：转化和治疗研究

基本信息

批准号：
7502713
负责人：
FENG C. ZHOU
金额：
$ 23.54万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7502713
关键词：
Address Adolescent Adopted Affect Africa Alcohol consumption Alcohol-Related Neurodevelopmental Disorder Alcohols Algorithms Alzheimer&apos s Disease Animal Model Animals Basic Science Behavioral Binding Sites Biology Birth Blood alcohol level measurement Bone and Cartilage Funding Brain Brain imaging C57BL/6 Mouse CDKN1A gene Cell Death Cells Characteristics Child Choline Clinical Clinical Research Clinical Sciences Collaborations Computational algorithm Computer software Computer-Assisted Image Analysis Consumption Count Data Development Diagnosis Diagnostic Diet Dietary Intervention Diffusion Diffusion Magnetic Resonance Imaging Dimensions Disruption Dissociation Dose Drug Design Dysmorphology Early Diagnosis Early Intervention Early identification Elements Embryo Emotional Ethanol Ethnic group Evaluation Experimental Animal Model Face Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Fetal Alcohol Syndrome Fiber Frequencies Functional disorder Funding Future Genetic Polymorphism Gestational Age Goals Growth Hippocampus (Brain)Human Image Image Analysis Imaging technology Impairment Individual Infant Infant Development Informal Social Control Informatics Inherited Intervention Knowledge Language Language Development Length Life Liquid substance Los Angeles Machine Learning Magnetic Resonance Imaging Measurement Measures Mental Retardation Methods Mission Modeling Morphology Moscow Mothers Mus NAPVSIPQ peptide Neonatal Nerve Degeneration Nerve Fibers Neural Cell Adhesion Molecule L1 Neurobiology Neurons New Mexico Oral Outcome Pathway interactions Patient currently pregnant Pattern Pattern Recognition Peptides Performance Phenotype Pilot Projects Play Population Pregnancy Prevalence Principal Investigator Rattus Recording of previous events Request for Applications Research Research Personnel Research Project Grants Resolution Resource Sharing Role Sampling Schools Sensitivity and Specificity Sheep Short-Term Memory Signal Pathway Signal Transduction Site Skeleton Source Specificity Staging Structure Sum Supplementation Surface System Technology Testing Therapeutic Therapeutic Agents Three-Dimensional Imaging Time Toddler Ukraine Ultrasonography Variant Vibrissae Western World Woman Work X-Ray Computed Tomography alcohol effect alcohol exposure alcohol sensitivity analog brain behavior brain morphology brain volume clinical application cognitive control craniofacial critical developmental period data integration day design digital imaging drinking face bone structure fetal follow-up human study image reconstruction improved in utero infancy literacy morphometry morris water maze mouse model multidisciplinary neurobehavioral neurochemistry neuroimaging neurotrophic factor northern plains novel oncoprotein p21 peptide analog postnatal prenatal prevent programs prospective relating to nervous system sensory cortex social tomography translational study young adult

项目摘要

DESCRIPTION (provided by applicant): Fetal alcohol syndrome (FAS) occurs in children born to women who drink alcohol heavily during pregnancy and is one of the leading non-hereditary causes of mental retardation in the Western World. It is estimated that the prevalence of FAS in the general U.S. population is between 0.5 and 2.0 per 1,000 births, while the undiagnosed population with variable facial and brain dysmorphology described as fetal alcohol spectrum disorder (FASD) is estimated to be 10 times higher. The difficulty in the diagnosis of FASD involves misdiagnosis due to the presence or absence of the typical facial dysmorphology in association with brain dysfunction. Accurate diagnosis is further complicated by the lack of information about the contribution of dose, frequency, and timing of alcohol exposure during pregnancy to variation in facial dysmorphology. In this project, a mouse model that models human consumption and is known to produce FAS-like features resulting from prenatal alcohol exposure, will be used to test the effects of differences in dose and timing of alcohol exposure on face and brain development. A combination of 3D imaging that includes Micro-video and micro-resonance imaging (MRI) will be used to capture the detailed facial structure, micro-computational tomography (Micro-CT) to capture the underlying facial bone, MRI for detailed brain dimensions, and diffusion tensor imaging (DTI) for nerve fiber tracks in the fetal period. A novel computational program will be compiled to detect features specifically as function of alcohol exposure. The association and dissociation of facial and brain dysmorphology as a function of dose and timing of alcohol exposure will be analyzed to better inform the diagnosis of FAS/ FASD. These studies will be a collaboration sharing resources and methods and will be performed across both Basic and Clinical Science components in consortium effort. To date there is no cure for FAS/FASD, which is a life long ordeal from the birth. Experimental tests, using the above model and setting, of trophic peptides which have been known to prevent neurodegeneration in trials for Alzheimer Disease and protect cell death in embryonic stage, have been partially tested in the embryonic period to show protection against the alcohol-induced retardation. The new studies will test whether the trophic peptides can prevent alcohol-induced brain and facial dysmorphology as well as behavioral impairment known to occur in FAS.

描述（由申请人提供）：胎儿酒精综合症（FAS）发生在怀孕期间大量饮酒的妇女所生的孩子中，是西方世界智力低下的主要非遗传性原因之一。据估计，美国普通人群中 FAS 的患病率在每 1,000 名新生儿中 0.5 至 2.0 人之间，而具有可变面部和大脑畸形（被称为胎儿酒精谱系障碍 (FASD)）的未确诊人群的患病率估计要高出 10 倍。 FASD 的诊断困难包括由于是否存在与脑功能障碍相关的典型面部畸形而导致误诊。由于缺乏有关怀孕期间饮酒的剂量、频率和时间对面部畸形变化的影响的信息，准确诊断变得更加复杂。在这个项目中，小鼠模型模拟了人类的消费，并且已知会因产前酒精暴露而产生类似 FAS 的特征，该模型将用于测试酒精暴露剂量和时间差异对面部和大脑发育的影响。包括微视频和微共振成像 (MRI) 在内的 3D 成像组合将用于捕获详细的面部结构，微计算断层扫描 (Micro-CT) 用于捕获底层面部骨骼，MRI 用于捕获详细的大脑尺寸，以及胎儿时期神经纤维轨迹的弥散张量成像（DTI）。将编译一个新颖的计算程序来检测专门作为酒精暴露函数的特征。我们将分析面部和大脑畸形的关联和分离与酒精暴露剂量和时间的函数关系，以更好地为 FAS/FASD 的诊断提供信息。这些研究将是一项共享资源和方法的合作研究，并将在基础科学和临床科学领域共同努力进行。迄今为止，FAS/FASD 尚无治愈方法，从出生起就是一种终生的折磨。使用上述模型和设置对营养肽进行实验测试，已知营养肽在阿尔茨海默病试验中可预防神经变性并保护胚胎期细胞死亡，已在胚胎期进行了部分测试，以显示对酒精引起的发育迟缓的保护作用。新研究将测试营养肽是否可以预防酒精引起的大脑和面部畸形以及已知发生在 FAS 中的行为障碍。