Fetal ethanol-induced behavioral deficits: Mechanisms, diagnoses and intervention

胎儿乙醇引起的行为缺陷：机制、诊断和干预

• 批准号: 8298952
• 负责人: Daniel D. Savage
• 金额: $ 46.01万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8298952
• 关键词: Achievement; Address; Administrator; Adolescent; Advisory Committees; Advocacy; Affect; Alcohols; Animal Testing; Area; Arizona; Award; Basic Science; Behavior; Behavioral; Biological Markers; Brain Injuries; Brain region; Cancer Center Planning Grant; Child; Clinic; Clinical; Clinical Research; Communication; Complement; Complex; Development; Diagnosis; Electronics; Ensure; Environment; Epidemiology; Epigenetic Process; Ethanol; Fellowship; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Fetal alcohol effects; Foundations; Funding; Funding Mechanisms; Future; Gene Expression Regulation; Genetic Variation; Goals; Grant; Health Sciences; Hippocampus (Brain); Human; Human Resources; Individual; Infant; Information Management; Institutes; Intervention; Investigation; Knowledge; Leadership; Learning; Life; Memory; Modeling; Monitor; Mothers; National Institute on Alcohol Abuse and Alcoholism; Nature; Neonatal Alcohol Exposure; Neurotransmitters; New Mexico; Newsletter; Outcome; Philosophy; Pilot Projects; Positioning Attribute; Post-Traumatic Stress Disorders; Pregnancy; Prevention; Rattus; Recording of previous events; Reporting; Research; Research Personnel; Research Project Grants; Rodent; Schools; Scientist; Secure; Series; Services; Societies; Supervision; Symptoms; Synaptic plasticity; System; TNFRSF5 gene; Texas; Therapeutic Agents; Translational Research; United States; Universities; Work; alcohol exposure; alcohol research; base; behavior test; data sharing; drinking; effective intervention; fetal; fetal diagnosis; human subject; meetings; multidisciplinary; neurobehavioral; neurodevelopment; neurogenesis; neuroimaging; neuropsychological; northern plains; novel; novel therapeutics; offspring; operation; patient population; pre-clinical; pre-clinical research; preclinical study; programs; research study; symposium; web page

DESCRIPTION (provided by applicant): The New Mexico Alcohol Research Center (NMARC) is a comprehensive, multidisciplinary program focused on fetal alcohol-related behavioral deficits. NMARC's prevailing philosophy is that significant progress towards the dual goals of better diagnoses and inventions for the behavioral deficits associated with Fetal Alcohol Spectrum Disorders (FASD) requires a well-coordinated effort integrating basic research advances that elucidate the mechanistic consequences of fetal ethanol exposure with combined neuropsychological and functional neuroimaging studies in human subjects with FASD. A research center organization that maximizes the coordination and communication across lines of investigation provides the best long-term prospect for overcoming the ongoing challenges of diagnosing fetal alcohol-induced behavioral deficits and devising more effective interventions to ameliorate these deficits. The NMARC is a composite of established fetal alcohol research investigators with a history of collaborative research interactions complemented by the addition of outstanding investigators from other fields whose expertise and contributions can synergize the center's research environment and facilitate progress towards achieving NMARC's strategic objectives. The strategic objectives of the NMARC program are to: 1) Advance our understanding of the teratogenic consequences of fetal ethanol exposure on the neurobiologic mechanisms that negatively impact behavior, both in rodents and humans, 2) develop more effective approaches for diagnosing subjects with FASD, through the use of combined neurobehavioral and functional neuroimaging assessments, as well as through the prospect of developing more sensitive and reliable biomarkers capable of detecting functional brain damage earlier in life, and 3) develop more effective interventions for fetal alcohol-related behavioral deficits. More efficacious interventions may require a combination of neurobehavioral, educational and pharmacotherapeutic approaches to ameliorate the often subtle, but long-lasting impact of these deficits on affected offspring. This NMARC P20 application consists of seven components including two cores (Administrative and Pilot Projects) and five "R03-level" Developmental Research components. Each of the three preclinical research components, the two clinical projects and the two pilot projects represent novel experimental approaches that will address at least one of the three strategic objectives of mechanisms, diagnoses or interventions. Likewise, a "pipeline" of future pilot project ideas described in the Pilot Project Core ensures continued pursuit of the NMARC's strategic objectives over the five year P20 project period. Oversight of the NMARC operation will be provided by the Administrative Core and the NMARC Executive Committee. Assessment of and advocacy for the NMARC's achievements along with guidance in operational matters will be provided by an Internal Advisory Committee consisting of five senior administrators in the UNM's Health Science Center, Main Campus and The MIND Institute. An External Advisory Committee of three internationally renowned fetal alcohol researchers will advise the NMARC Executive Committee and component investigators and monitor NMARC's progress towards the achievement of its specific aims and strategic objectives.

描述（由申请人提供）：新墨西哥酒精研究中心（NMARC）是一项全面的，多学科的计划，重点介绍了与胎儿酒精相关的行为缺陷。 NMARC的流行哲学是，朝着与胎儿酒精谱系障碍相关的行为缺陷（FASD）的行为缺陷的双重目标的重大进展（FASD）需要良好的协调努力，以整合基础研究的努力，以阐明胎儿乙醇暴露的机械性后果与与人类的合并神经心理学和功能性研究相结合。一个研究中心组织，最大程度地提高调查范围的协调和交流，为克服诊断胎儿酒精引起的行为缺陷的持续挑战提供了最佳的长期前景，并设计了更有效的干预措施以改善这些缺陷。 NMARC是成熟的胎儿酒精研究研究者的合成，具有协作研究史的历史，并补充了来自其他领域的杰出研究人员的专业知识和贡献可以协同中心的研究环境，并促进实现NMARC的战略目标的进步。 The strategic objectives of the NMARC program are to: 1) Advance our understanding of the teratogenic consequences of fetal ethanol exposure on the neurobiologic mechanisms that negatively impact behavior, both in rodents and humans, 2) develop more effective approaches for diagnosing subjects with FASD, through the use of combined neurobehavioral and functional neuroimaging assessments, as well as through the prospect of developing more sensitive and reliable生物标志物能够在生命中检测到功能性脑损伤，以及3）针对胎儿酒精相关的行为缺陷产生更有效的干预措施。更有效的干预措施可能需要将神经行为，教育和药物治疗方法结合在一起，以改善这些缺陷对受影响后代的经常微妙但持久的影响。该NMARC P20应用程序由七个组件组成，其中包括两个核心（行政和试点项目）和五个“ R03级”发展研究组件。三个临床前研究组件中的每一个，两个临床项目和两个试点项目都代表新的实验方法，这些方法将至少解决机制，诊断或干预措施的三种战略目标。同样，在飞行员项目核心中描述的未来试点项目思想的“管道”确保在五年P20项目期间继续追求NMARC的战略目标。对NMARC操作的监督将由行政核心和NMARC提供 执行委员会。内部咨询委员会将对NMAR的成就的评估和倡导以及运营事务的指导，由UNM的健康科学中心，主要校园和Mind Institute组成的五名高级管理人员组成。由三名国际知名胎儿酒精研究人员组成的外部咨询委员会将为NMARC执行委员会和组件调查人员提供建议，并监控NMARC在实现其具体目标和战略目标方面的进步。

项目成果

Effects of the cognition-enhancing agent ABT-239 on fetal ethanol-induced deficits in dentate gyrus synaptic plasticity.

认知增强剂 ABT-239 对胎儿乙醇诱导的齿状回突触可塑性缺陷的影响。

• DOI: 10.1124/jpet.109.165027
• 发表时间: 2010
• 期刊: The Journal of pharmacology and experimental therapeutics
• 作者: Varaschin,RafaelK;Akers,KatherineG;Rosenberg,MartinaJ;Hamilton,DerekA;Savage,DanielD
• 通讯作者: Savage,DanielD

Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density.

乙醇引起的胎盘和胎儿脑皮质膜联蛋白 A4 和脑海绵状血管瘤蛋白 3 的改变与胎儿皮质 VEGF 受体结合和微血管密度的减少有关。

• DOI: 10.3389/fnins.2020.00519
• 发表时间: 2020
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Savage,DanielD;Rosenberg,MartinaJ;Coquet,Laurent;Porch,MorganW;Allen,NyikaA;Roux,Christian;Aligny,Caroline;Jouenne,Thierry;Gonzalez,BrunoJ
• 通讯作者: Gonzalez,BrunoJ

Patterns of social-experience-related c-fos and Arc expression in the frontal cortices of rats exposed to saccharin or moderate levels of ethanol during prenatal brain development.

• DOI: 10.1016/j.bbr.2010.05.048
• 发表时间: 2010-12-06
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Hamilton, Derek A.;Candelaria-Cook, Felicha T.;Akers, Katherine G.;Rice, James P.;Maes, Levi I.;Rosenberg, Martina;Valenzuela, C. Fernando;Savage, Daniel D.
• 通讯作者: Savage, Daniel D.

Facilitating neuronal connectivity analysis of evoked responses by exposing local activity with principal component analysis preprocessing: simulation of evoked MEG.

• DOI: 10.1007/s10548-012-0250-1
• 发表时间: 2013-04
• 期刊: BRAIN TOPOGRAPHY
• 影响因子: 2.7
• 作者: Gao, Lin;Zhang, Tongsheng;Wang, Jue;Stephen, Julia
• 通讯作者: Stephen, Julia

Focus on: biomarkers of fetal alcohol exposure and fetal alcohol effects.

重点关注：胎儿酒精暴露和胎儿酒精影响的生物标志物。

• 发表时间: 2011
• 期刊: Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism
• 作者: Bakhireva,LudmilaN;Savage,DanielD
• 通讯作者: Savage,DanielD