Regulation of the Antioxidant Glutathione: In the Cerebral Cortex and the Relationship with Peripheral Tissues

Glutathione (GSH) is a ubiquitous thiol tripeptide that is well known for its antioxidant role in reducing oxidative stress and maintaining redox balance. Oxidative stress occurs when there is an imbalance between reactive oxygen species (ROS) and antioxidants in favor of ROS production, which have been implicated in disease. Previous studies have utilized inbred mice models to identify canonical GSH genes influencing GSH regulation, however, these findings do not reflect the genetic diversity of the human population. Recent studies suggest that GSH regulation is governed by tissue-specific novel genes, yet there is little understanding of the genetic mechanisms that regulate GSH levels in the brain. To address this knowledge gap, we utilized the Diversity Outbred (DO) mouse stock, which models a diverse genetic profile comparable to humans, to (1) compare levels and regulation of glutathione in the brain to other major tissues and (2) investigate genes in the genome influencing brain glutathione regulation.