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(由申请者提供)：新墨西哥州酒精研究中心(NMARC)是一个全面的、多学科的项目，专注于胎儿酒精相关的行为缺陷。NMARC的主要理念是，要实现更好地诊断和发明与胎儿酒精光谱障碍(FASD)相关的行为缺陷的双重目标，需要良好协调的努力，将阐明胎儿酒精暴露的机制后果的基础研究进展与人类FASD受试者的神经心理和功能神经成像研究相结合。一个最大限度地协调和沟通各调查领域的研究中心组织，为克服诊断胎儿酒精诱导的行为缺陷和设计更有效的干预措施改善这些缺陷的持续挑战提供了最好的长期前景。NMARC是由成熟的胎儿酒精研究人员组成的复合体，具有合作研究互动的历史，并补充了来自其他领域的杰出研究人员，他们的专业知识和贡献可以协同中心的研究环境，促进实现NMARC战略目标的进展。NMARC计划的战略目标是：1)促进我们对胎儿酒精暴露对啮齿动物和人类行为产生负面影响的神经生物学机制的致畸后果的理解；2)通过结合神经行为和功能神经成像评估，以及通过开发能够检测生命早期功能性脑损伤的更敏感和可靠的生物标记物的前景，开发更有效的方法来诊断FASD受试者；以及3)开发更有效的干预措施来治疗胎儿酒精相关的行为缺陷。更有效的干预措施可能需要神经行为、教育和药物治疗方法的结合，以改善这些缺陷对受影响后代的往往微妙但长期的影响。这个NMARC P20应用程序由七个组件组成，包括两个核心(管理和试验项目)和五个“R03级”开发研究组件。三个临床前研究部分、两个临床项目和两个试点项目中的每一个都代表了新的实验方法，将至少解决机制、诊断或干预三个战略目标中的一个。同样，试点项目核心中描述的未来试点项目想法的“管道”确保在五年P20项目期内继续追求NMARC的战略目标。对NMARC运作的监督将由行政核心和NMARC提供 执行委员会。对NMARC成就的评估和宣传以及业务事项的指导将由一个内部咨询委员会提供，该委员会由新墨西哥州卫生科学中心、主校区和心理研究所的五名高级管理人员组成。一个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向NMARC执行委员会和组件调查人员提供建议，并监督NMARC在实现其特定目标和战略目标方面的进展。

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

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.

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

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