Testing the KYNA Hypothesis in Translationally Relevant Studies using Miniature Pigs

NIH RePORTER · NIH · P50 · $794,425 · view on reporter.nih.gov ↗

Abstract

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

Key facts

NIH application ID
10425362
Project number
5P50MH103222-09
Recipient
UNIVERSITY OF MARYLAND BALTIMORE
Principal Investigator
PETER V. KOCHUNOV
Activity code
P50
Funding institute
NIH
Fiscal year
2022
Award amount
$794,425
Award type
5
Project period
2014-05-09 → 2024-06-30