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: 10425362
• 负责人: PETER V. KOCHUNOV
• 金额: $ 79.44万
• 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/10425362
• 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; kynurenine aminotransferase II; lateral ventricle; multimodality; neurochemistry; neuroimaging; neuropsychiatry; offspring; population based; porcine model; prenatal; prevent; schizophrenia risk; 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摘要 基于在这个Conte中心进行的所有研究的中心假设，项目2将建立一个两个 发展可分离的侮辱（“双重打击”）模型，以研究定时干预的影响， 犬尿氨酸氨基转移酶（KAT）II抑制剂。该项目将把项目1（小鼠）的知识与 项目3和4（人类）通过中间转化动物模型-小型猪（Sus scrofa 南极洲）。小型猪有着巨大的脑回，发育轨迹与人类相似， 为人类同等的侵入性神经科学技术和大脑神经成像提供了机会， 评估。项目2将反映项目1中的实验， 犬尿烯酸（KYNA）在怀孕中期（第一次击中）和青春期（第二次击中）使用 神经成像和电生理方案与项目3和4中使用的方案相同。评估 该项目中开发的协议、分析工作流程和多模式大脑图谱将在 努力加速在神经精神病学研究中使用猪模型。 1