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Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice

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 i...

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Autores principales: Qiu, Li-Li, Luo, Dan, Zhang, Hui, Shi, Yun S., Li, Yan-Jun, Wu, Dan, Chen, Jiang, Ji, Mu-Huo, Yang, Jian-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062642/
https://www.ncbi.nlm.nih.gov/pubmed/27790135
http://dx.doi.org/10.3389/fnagi.2016.00234
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author Qiu, Li-Li
Luo, Dan
Zhang, Hui
Shi, Yun S.
Li, Yan-Jun
Wu, Dan
Chen, Jiang
Ji, Mu-Huo
Yang, Jian-Jun
author_facet Qiu, Li-Li
Luo, Dan
Zhang, Hui
Shi, Yun S.
Li, Yan-Jun
Wu, Dan
Chen, Jiang
Ji, Mu-Huo
Yang, Jian-Jun
author_sort Qiu, Li-Li
collection PubMed
description 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 vitro were 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.
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spelling pubmed-50626422016-10-27 Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice Qiu, Li-Li Luo, Dan Zhang, Hui Shi, Yun S. Li, Yan-Jun Wu, Dan Chen, Jiang Ji, Mu-Huo Yang, Jian-Jun Front Aging Neurosci Neuroscience 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 vitro were 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. Frontiers Media S.A. 2016-10-13 /pmc/articles/PMC5062642/ /pubmed/27790135 http://dx.doi.org/10.3389/fnagi.2016.00234 Text en Copyright © 2016 Qiu, Luo, Zhang, Shi, Li, Wu, Chen, Ji and Yang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Qiu, Li-Li
Luo, Dan
Zhang, Hui
Shi, Yun S.
Li, Yan-Jun
Wu, Dan
Chen, Jiang
Ji, Mu-Huo
Yang, Jian-Jun
Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice
title Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice
title_full Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice
title_fullStr Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice
title_full_unstemmed Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice
title_short Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice
title_sort nox-2-mediated phenotype loss of hippocampal parvalbumin interneurons might contribute to postoperative cognitive decline in aging mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062642/
https://www.ncbi.nlm.nih.gov/pubmed/27790135
http://dx.doi.org/10.3389/fnagi.2016.00234
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