title: NOX2 Mediated-Parvalbumin Interneuron Loss Might Contribute to Anxiety-Like and Enhanced Fear Learning Behavior in a Rat Model of Post-Traumatic Stress Disorder.
abstract: Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, yet the precise mechanisms underlying PTSD remains largely to be determined. Using an animal model of PTSD induced by a single prolonged stress (SPS), we assessed the role of hippocampal nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and parvalbumin (PV) interneurons in the development of PTSD symptoms. In the present study, behavioral tests were performed by the open field (day 13 after SPS) and fear conditioning tests (days 13 and 14 after SPS). For the interventional study, rats were chronically treated with a NADPH oxidase inhibitor apocynin either by early or delayed administration. The levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, malondialdehyde, superoxide dismutase, NOX2, 4-hydroxynonenal, and PV in the hippocampus were measured at the indicated time points. In the present study, we showed that SPS rats displayed anxiety-like and enhanced fear learning behavior, which was accompanied by the increased expressions of malondialdehyde, IL-6, NOX2, 4-hydroxynonenal, and decreased PV expression. Notably, early but not delayed treatment with apocynin reversed all these abnormalities after SPS. In conclusion, our results provided evidence that NOX2 activation in the hippocampus, at least in part, contributes to oxidative stress and neuroinflammation, which further results in PV interneuron loss and consequent PTSD symptoms in a rat model of PTSD induced by SPS.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lin-Dong
authors.initials: LD
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Xing-Ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China. jimuhuo2009@sina.com.
authors.forename: Mu-Huo
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China. Yuanhm667@126.com.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Yuan
mesh_terms: D000098:Acetophenones / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000473:pathology*; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005239:Fear; D006624:Hippocampus / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism*; D007858:Learning; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D000074662:NADPH Oxidase 2 / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology*; D013315:Stress, Psychological / Q000473:pathology
chemical_list: D000098:Acetophenones; D000447:Aldehydes; D015850:Interleukin-6; D010320:Parvalbumins; D008315:Malondialdehyde; C056165:acetovanillone; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; C027576:4-hydroxy-2-nonenal
keywords: Anxiety; Fear learning; NADPH; PV; Single prolonged stress