To investigate possible causes of increases in oxidative stress and concomitant PV-IR decrease in the PV-positive interneurons, we evaluated the expression levels of the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor γ coactivator α). PGC-1α, a master regulator of mitochondrial energy metabolism and anti-oxidation (22), is activated by ROS overproduction and stimulates the transcription of ROS-detoxifying enzyme genes (23). Previous study has also suggested that PGC-1α appears to be necessary and sufficient for neuronal PV expression (24). First, to verify the PV interneuron-predominant expression of PGC-1α, we performed double in situ hybridization using DIG-labeled PGC-1α mRNA antisense probe and DNP-labeled PV mRNA antisense probes (Figure 5A, B). In wild-type control brains, almost all the PV-containing cells were PGC-1α-positive in S1 cortex (97.5% of PV cells in layer II/III and 100% in layer IV-VI), while of the total population of PGC-1α positive cells the majority were PV positive (88.5%, 22.5%, and 64.4% in layer II/III, layer IV/V, and layer VI, respectively in Figure 5B). Interestingly, PGC-1α mRNA signals were dramatically reduced following PWSI in the cortex of KO mice (Figure 5C). Quantitative
