Testing the KYNA Hypothesis in Translationally Relevant Studies using Miniature Pigs

使用小型猪在转化相关研究中检验 KYNA 假设

• 批准号: 10016395
• 负责人: PETER V. KOCHUNOV
• 金额: $ 76.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-09 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10016395
• 关键词: Adolescence; Adolescent; Affect; Age; Animal Model; Animals; Area; Atlases; Brain; Cerebrum; Chronic; Cognitive; Communities; Complement; Data; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Domestic Pig; Electroencephalography; Electrophysiology (science); Event; Evoked Potentials; Exhibits; Exposure to; Family suidae; Goals; Hippocampus (Brain); Human; Image; Individual; Intervention; Knowledge; Kynurenic Acid; Kynurenine; Magnetic Resonance Imaging; Measurement; Measures; Modeling; Mus; Neurosciences; Pattern; Pharmacology; Protocols documentation; Research; Rest; Schizophrenia; Second Pregnancy Trimester; Structure; Techniques; Testing; Thick; Time; adolescent brain development; attenuation; base; cognitive function; experimental study; gray matter; high risk; inhibitor/antagonist; kynurenine aminotransferase II; lateral ventricle; multimodality; neurochemistry; neuroimaging; neuropsychiatry; offspring; population based; prenatal; prevent; source localization; white matter

Project 2 Summary Based on the central hypothesis of all research conducted in this Conte Center, Project 2 will establish a two developmentally-dissociable insult (“double-hit”) model to study the effects of timed intervention with a kynurenine aminotransferase (KAT) II inhibitor. This project will bridge knowledge from Project 1 (mice) to Projects 3 and 4 (humans) through an intermediary translational animal model - miniature pigs (Sus scrofa domestica). Miniature pigs have large gyrencephalic brains and a developmental trajectory similar to humans, providing the opportunity for human-equivalent invasive neuroscience techniques and neuroimaging brain assessments. Project 2 will mirror the experiments in Project 1 by mapping the effects of chronic elevations in kynurenic acid (KYNA) during the second trimester of pregnancy (1st hit) and in adolescence (2nd hit) using neuroimaging and electrophysiology protocols identical to those used in Projects 3 and 4. The assessment protocols, analytical workflows and multimodal brain atlases developed in this project will be disseminated in an effort to accelerate the use of pig models in neuropsychiatric research. 1

项目2总结 根据该 Conte 中心进行的所有研究的中心假设，项目 2 将建立两个 发育分离性侮辱（“双重打击”）模型，用于研究定时干预的效果 该项目将连接项目 1（小鼠）的知识。 项目 3 和 4（人类）通过中介转化动物模型 - 小型猪（Sus scrofa） 小型猪具有较大的脑环和与人类相似的发育轨迹， 为相当于人类的侵入性神经科学技术和大脑神经成像提供机会 项目 2 将通过绘制长期海拔升高的影响来反映项目 1 中的实验。 犬尿酸 (KYNA) 在妊娠中期（第一次打击）和青春期（第二次打击）使用 神经影像和电生理学协议与项目 3 和 4 中使用的协议相同。 该项目开发的方案、分析工作流程和多模式脑图谱将在 努力加速猪模型在神经精神病学研究中的应用。 1