Neuroanatomical/Functional Correlates in an FASD Model

FASD 模型中的神经解剖学/功能相关性

• 批准号: 8536198
• 负责人: Scott Parnell
• 金额: $ 22.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536198
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Adverse effects; Attention; Behavioral; Biological Markers; Birth; Brain; Brain region; Cerebellum; Cognitive; Collaborations; Corpus Callosum; Data; Defect; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease model; Dose; Dysmorphology; Embryo; Environment; Ethanol; Exhibits; Exposure to; Eye; Fertilization; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Alcohol Syndrome; Fiber; First Pregnancy Trimester; Foundations; Future; Goals; Growth; Hippocampus (Brain); Human; Imaging Techniques; Imaging technology; Individual; Knowledge; Learning; Literature; Long-Term Effects; Magnetic Resonance Imaging; Mentorship; Methods; Motor; Mus; Nervous system structure; Neural Pathways; North Carolina; Pathology; Pathway interactions; Pattern; Phenotype; Pregnancy; Prevention; Reporting; Research; Research Training; Resolution; Sensory; Severities; Solid; Specimen; Staging; Structure; Testing; Time; Training; Universities; Work; alcohol effect; alcohol exposure; behavior test; brain pathway; brain tract; career; design; experience; fetal; mouse model; offspring; postnatal; prenatal; pup; research study

Among the most common, yet devastating, effects of prenatal ethanol exposure are those that involve the developing brain. While both structural and functional abnormalities of the brain have been described in individuals with Fetal Alcohol Syndrome (FAS)/Fetal Alcohol Spectrum Disorders (FASD), gaps remain in our understanding of the full range of these defects and of expected structural/functional correlates. Following up on the previous work of others, as well as the applicant's recent research, the experiments proposed herein are designed to examine the long-term effects of early gestational exposure on both brain structure and function and to provide correlative data. Overall, the proposed work will test the hypothesis that ethanol exposure at early gestational stages (gestational day [GD] 8 in mice; equivalent to the fourth week post fertilization in humans) results in a correlative pattern of brain dysmorphology and neurofunctional deficits that persists into adulthood. The proposed work will employ a mouse FASD model, state of the art high-resolution Magnetic Resonance Imaging (MRI), Diffusion Tensor Imaging (DTI), and a battery of cognitive, sensory, motor and other behavioral tests. In addition to furthering the applicant's training in MRI/DTI techniques, analyses and interpretation, the experiments and educational opportunities outlined in this proposal will greatly enhance the candidate's knowledge and understanding of methods designed to characterize neurofunctional phenotypes. Promise for the successful completion of this work is provided by the exceptional research environment of the University of North Carolina - Chapel Hill and of Duke University, mentorship by and collaboration with experts in the FASD field (Dr. K Sulik), behavioral analyses (Dr. S Moy), and imaging technologies (Drs A Johnson and M Styner), as well as the applicant's previous FASD research experience. Having illustrated the utility of high resolution MRI for discovery of ethanol-induced brain dysmorphology in fetal mice (Parnell et al, 2009), the proposed work will extend these analyses into postnatal stages. This work will be conducted by addressing 3 sub-hypotheses and the associated specific aims as follows: SPECIFIC AIM #1 will test the hypothesis that acute ethanol exposure on GD 8 will produce long-term morphological effects on specific regions of the mouse brain. The experiments for this aim will utilize high-resolution MRI and will entail analyses of the brains of postnatal day (PD) 12, 30, and 90 mice. SPECIFIC AIM #2 will test the hypothesis that this same ethanol exposure paradigm will alter the interconnecting neural pathways of the brain. Fiber tracts of the brains of PD 12, 30, and 90 mice will be assessed utilizing DTI. SPECIFIC AIM #3 will test the hypothesis that acute GD 8 ethanol exposure will result in neurofunctional abnormalities in adolescent and adult mice that are consistent with the observed dysmorphology. The results of these studies will provide important data regarding the long-term consequences of early gestational ethanol exposure and will, undoubtedly, promise to inform FASD diagnosis and prevention efforts. Additionally, the research and training described in this proposal will provide a solid foundation for both future studies regarding ethanol's teratogenesis, and the candidate's goal of pursuing a career as an academician.

产前酒精暴露最常见但也是最具破坏性的影响是那些涉及发育中的大脑的影响。