Testing the KYNA Hypothesis in Translationally Relevant Studies using Miniature Pigs

项目2摘要 基于在这个研究中心进行的所有研究的中心假设，项目2将建立两个 发展-分离性侮辱(“双击式”)模型研究定时干预的效果 犬尿氨酸转氨酶(KAT)II抑制剂。该项目将把知识从项目1(MICE)连接到 项目3和4(人类)通过中间翻译动物模型--微型猪(Sus Scrofa) 家庭式)。小型猪有巨大的脑回，其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神经成像脑提供机会 评估。项目2将通过绘制慢性海拔高度的影响来反映项目1中的实验 妊娠中期(第一次)和青春期(第二次)使用犬尿酸(KYNA) 神经成像和电生理学方案与项目3和4中使用的方案相同。 在该项目中开发的方案、分析工作流程和多模式脑图谱将在 加快在神经精神病学研究中使用猪模型的努力。 1

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