title: Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice.
abstract: Postoperative cognitive decline (POCD) is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated-abnormalities in parvalbumin (PV) interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in 16-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO). Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide (LPS)in vitrowere used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β (IL-1β), markers of oxidative stress and NADPH oxidase 2 (Nox2) in the hippocampus. In addition, LPS exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived reactive oxygen species (ROS) production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice.
authors: Zhongda Hospital, School of Medicine, Southeast University Nanjing, China.
authors: Li-Li
authors: LL
authors: Qiu
authors: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors: Dan
authors: D
authors: Luo
authors: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors: Hui
authors: H
authors: Zhang
authors: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University Nanjing, China.
authors: Yun S
authors: YS
authors: Shi
authors: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University Nanjing, China.
authors: Yan-Jun
authors: YJ
authors: Li
authors: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University Nanjing, China.
authors: Dan
authors: D
authors: Wu
authors: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University Nanjing, China.
authors: Jiang
authors: J
authors: Chen
authors: Zhongda Hospital, School of Medicine, Southeast University Nanjing, China.
authors: Mu-Huo
authors: MH
authors: Ji
authors: Zhongda Hospital, School of Medicine, Southeast University Nanjing, China.
authors: Jian-Jun
authors: JJ
authors: Yang
keywords: Nox2; aging; apocynin; hippocampus; parvalbumin; postoperative cognitive decline