Supplement 1), suggesting that NADPH oxidase Nox2 is not the main source of the elevated ROS in our animal model. We postulate that the impaired antioxidant capacity of PV interneurons is due to PGC-1α down-regulation enhanced ROS levels in response to social isolation. Alternatively, albeit not mutually exclusive, we do not exclude the possible contribution of other Nox family proteins to the ROS increase in PWSI KO mice. For example, NADPH oxidase Nox4 mRNA level appeared to be elevated in 16-week-old KO mice; otherwise at the level near the detection limit in the fGluN1 controls (Figure S5F in Supplement 1). Nox4 is known to produce hydrogen peroxide (46), cell membrane-permeable ROS (47), which might cause ROS elevation in many cell-types (Figure 1). Further study is necessary to clarify the cellular mechanisms of the ROS level elevation in the PWSI KO mice.
