PGC-1α is a master regulator of mitochondrial energy metabolism and anti-oxidation (22) and is known to work in concert with other proteins to drive the expression of ROS-detoxifying enzymes in response to ROS elevations (23). PGC-1α-mediated anti-oxidation is thus one possible anti-oxidation mechanism in PV neurons because it’s most highly concentrated in PV-positive neurons (32; Figure 5). Indeed, in KO mice after PWSI, we demonstrated down-regulation of cortical PGC-1α and several of its downstream targets important for antioxidant function. PGC-1α is also required for the normal expression of the calcium buffer PV (24); thus, as expected, decreases in PV expression accompanied decreases in PGC-1α in PWSI-exposed KO mice. Taken together, the data suggest that a decrease in PGC-1α abundance compromises multiple transcriptional pathways, augmenting oxidative stress in PV-containing fast-spiking neurons.
