title: 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.
abstract: 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.
authors: Department of Emergency, Ruijin Hospital North, School of Medicine, Shanghai Jiaotong University, 999 Xiwang Road, Jiading District, Shanghai 201801, PR China.
authors: Dong
authors: D
authors: Liang
authors: Department of Anesthesia, The 101st Hospital of PLA, Wuxi 214044, PR China.
authors: Guowei
authors: G
authors: Li
authors: Department of Anesthesia, The 101st Hospital of PLA, Wuxi 214044, PR China.
authors: Xingzhi
authors: X
authors: Liao
authors: Department of Anesthesia, The 101st Hospital of PLA, Wuxi 214044, PR China.
authors: Dawei
authors: D
authors: Yu
authors: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, PR China.
authors: Jing
authors: J
authors: Wu
authors: Department of Anaesthesiology, Teaching Hospital of Chengdu University of T.C.M, 39 Twelve Bridge Road, Jinniu District, Chengdu 610072, PR China. Electronic address: qiangzhiq80@sina.com.
authors: Mingqiang
authors: M
authors: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D002534:Hypoxia, Brain / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010320:Parvalbumins; D019255:NADPH Oxidases
keywords: Intermittent hypoxia; NOX2-derived oxidative stress; Neonatal rats; Parvalbumin-positive cells; Psychiatric anxiety