Sleep disruption elevates oxidative stress in parvalbumin-positive cells of the rat cerebral cortex. Harkness John H,Bushana Priyanka N,Todd Ryan P,Clegern William C,Sorg Barbara A,Wisor Jonathan P Sleep We used a novel automated sleep disruption (SD) apparatus to determine the impact of SD on sleep and molecular markers of oxidative stress in parvalbumin (PV) neurons in the rat prefrontal cortex (PFC). Rats were subjected to two 6 hr SD sessions from zeitgeber time (ZT) 0 to ZT6, one by the gentle handling method and the other by an automated agitator running the length of the rat's home cage floor (a novel SD method). The same rats were later subjected to a 12 hr SD session from ZT0 to ZT12. Sleep was disrupted with both methods, although rats slept less during gentle handling than during the automated condition. Immediately after both SD sessions, rats displayed compensatory sleep characterized by elevated slow-wave activity. We measured in the prelimbic prefrontal cortex (prelimbic PFC; 6 and 12 hr SD) and orbital frontal cortex (12 hr SD) the intensity of the oxidative stress marker, 8-oxo-2'-deoxyguanosine (8-oxo-dG) as well as the staining intensity of PV and the PV cell-associated perineuronal net marker, Wisteria floribunda agglutinin (WFA). In the prelimbic PFC, 6 hr SD increased the intensity of 8-oxo-dG, PV, and WFA. After 12 hr SD, the intensity of 8-oxo-dG was elevated in all neurons. PV intensity was elevated only in neurons colabeled with 8-oxo-dG or WFA, and no changes were found in WFA intensity. We conclude that in association with SD-induced sleep drive, PV neurons in the prelimbic PFC exhibit oxidative stress. 10.1093/sleep/zsy201

Developmental loss of parvalbumin-positive cells in the prefrontal cortex and psychiatric anxiety after intermittent hypoxia exposures in neonatal rats might be mediated by NADPH oxidase-2. Liang Dong,Li Guowei,Liao Xingzhi,Yu Dawei,Wu Jing,Zhang Mingqiang Behavioural brain research Sleep apnea is more frequently experienced in neonatal life. Here we investigated the causal contribution of NOX2-derived oxidative stress in the prefrontal cortex (PFC) to neurodevelopmental alterations and psychiatric anxiety in a neonatal rat model of sleep apnea. Neonatal postnatal day 5 (P5) rats were exposed to long-term intermittent hypoxia (LTIH) or room air (RA) for 10 days. In the PFC, we determined the impact (I) of LTIH exposures on NADPH oxidase-2 (NOX2) expression and oxidative stress (II) of pharmacological NOX2 inhibition on LTIH-induced neurodevelopmental alterations in the P14 and P49 rats. Endpoints were NOX2-derived oxidative stress, parvalbumin (PV)-positive cells (PV-cells) and psychiatric anxiety. The results showed neonatal LTIH exposures increased NOX2 expression in the PFC of P14 rats, which was accompanied with elevation of NOX activity. Neonatal LTIH exposures increased oxidative stress in cortical PV-cells characterized by elevation of 8-hydroxy-20-deoxyguanosine (8-OHDG) level and reduced PV immunoreactivity, PV-cell counts in the PFC of P14 and P49 rats. Neonatal LTIH exposures increased psychiatric anxiety levels in the P49 rats. Pretreatment of neonatal rats before each neonatal LTIH exposure with the antioxidant/NOX inhibitor apocynin prevented the reduced PV immunoreactivity, PV-cells loss in the PFC and development of anxiety-like behavior. Our data suggest that NOX2-derived oxidative stress might be involved in the developmental loss of PV-cells in the PFC and development of psychiatric anxiety for neonatal rats exposed to LTIH. 10.1016/j.bbr.2015.08.033