Cortical PV interneurons have unique fast-spiking properties involved in driving synchronous oscillatory activity (25–28). To maintain high frequency firing, PV neurons contain high concentrations of cytochrome oxidase c and a greater number of mitochondria than pyramidal cells (29). Mitochondria in these fast-spiking neurons produce much more ROS and ATP compared to other cell types. Thus, fast-spiking neurons are equipped with potent anti-oxidation mechanisms to counterbalance increased ROS production. In the present study, cortical PV interneurons in Ppp1r2-cre/fGluN1 KO mice that underwent PWSI showed prominent staining in response to 8-OH-dG and 4-HNE, markers of DNA oxidation and lipid peroxidation, respectively. Cortical PV immunoreactivity, but not calretinin or calbindin immunoreactivity, was also reduced following PWSI in KO mice, which is consistent with recent findings indicating that PV neurons are vulnerable to chronic stress (4,30,31). These results suggest that PV interneurons in KO animals are highly vulnerable to oxidative stress.
