A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

Postoperative cognitive dysfunction (POCD) is a common postoperative neurocognitive complication in elderly patients. However, the specific pathogenesis is unknown, and it has been demonstrated that neuroinflammation plays a key role in POCD. Recently, increasing evidence has proven that the locus c...

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Autores principales:	Jiayu Wang, Ying Zhou, Ke Li, Xiaofeng Li, Meimei Guo, Mian Peng
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	postoperative dysfunction locus coeruleus noradrenergic system neuroinflammation DSP-4 microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/1ce45f12aa6548cfa974cf54a36a56d9
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spelling	oai:doaj.org-article:1ce45f12aa6548cfa974cf54a36a56d92021-12-01T19:25:45ZA Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation1662-509910.3389/fnmol.2021.752838https://doaj.org/article/1ce45f12aa6548cfa974cf54a36a56d92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnmol.2021.752838/fullhttps://doaj.org/toc/1662-5099Postoperative cognitive dysfunction (POCD) is a common postoperative neurocognitive complication in elderly patients. However, the specific pathogenesis is unknown, and it has been demonstrated that neuroinflammation plays a key role in POCD. Recently, increasing evidence has proven that the locus coeruleus noradrenergic (LCNE) system participates in regulating neuroinflammation in some neurodegenerative disorders. We hypothesize that LCNE plays an important role in the neuroinflammation of POCD. In this study, 400 μg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected intracerebroventricularly into each rat 7 days before anesthesia/surgery to deplete the locus coeruleus (LC) noradrenaline (NE). We applied a simple laparotomy and brief upper mesenteric artery clamping surgery as the rat POCD model. The open field test, novel objection and novel location (NL) recognition, and Morris water maze (MWM) were performed to assess postoperative cognition. High-performance liquid chromatography (HPLC) was used to measure the level of NE in plasma and brain tissues, and immunofluorescence staining was applied to evaluate the activation of microglia and astrocytes. We also used enzyme-linked immune-sorbent assay (ELISA) to assess the levels of inflammatory cytokines and brain-derived neurotrophic factor (BDNF). Pretreatment with DSP-4 decreased the levels of systemic and central NE, increased the level of interleukin-6 (IL-6) in the plasma at 6 h after the surgery, decreased the concentration of IL-6 in the prefrontal cortex and hippocampus, and decreased the level of interleukin-1β (IL-1β) in the plasma, prefrontal cortex, and hippocampus at 1 week postoperatively. In addition, DSP-4 treatment attenuated hippocampal-dependent learning and memory impairment in rats with POCD, with a downregulation of the activation of microglia and astrocytes in the prefrontal cortex and hippocampus. In conclusion, these findings provide evidence of the effects of LCNE in modulating neuroinflammation in rats with POCD and provide a new perspective in the prevention and treatment of POCD.Jiayu WangYing ZhouKe LiXiaofeng LiMeimei GuoMian PengFrontiers Media S.A.articlepostoperative dysfunctionlocus coeruleus noradrenergic systemneuroinflammationDSP-4microgliaNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Molecular Neuroscience, Vol 14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	postoperative dysfunction locus coeruleus noradrenergic system neuroinflammation DSP-4 microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	postoperative dysfunction locus coeruleus noradrenergic system neuroinflammation DSP-4 microglia Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Jiayu Wang Ying Zhou Ke Li Xiaofeng Li Meimei Guo Mian Peng A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation
description	Postoperative cognitive dysfunction (POCD) is a common postoperative neurocognitive complication in elderly patients. However, the specific pathogenesis is unknown, and it has been demonstrated that neuroinflammation plays a key role in POCD. Recently, increasing evidence has proven that the locus coeruleus noradrenergic (LCNE) system participates in regulating neuroinflammation in some neurodegenerative disorders. We hypothesize that LCNE plays an important role in the neuroinflammation of POCD. In this study, 400 μg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected intracerebroventricularly into each rat 7 days before anesthesia/surgery to deplete the locus coeruleus (LC) noradrenaline (NE). We applied a simple laparotomy and brief upper mesenteric artery clamping surgery as the rat POCD model. The open field test, novel objection and novel location (NL) recognition, and Morris water maze (MWM) were performed to assess postoperative cognition. High-performance liquid chromatography (HPLC) was used to measure the level of NE in plasma and brain tissues, and immunofluorescence staining was applied to evaluate the activation of microglia and astrocytes. We also used enzyme-linked immune-sorbent assay (ELISA) to assess the levels of inflammatory cytokines and brain-derived neurotrophic factor (BDNF). Pretreatment with DSP-4 decreased the levels of systemic and central NE, increased the level of interleukin-6 (IL-6) in the plasma at 6 h after the surgery, decreased the concentration of IL-6 in the prefrontal cortex and hippocampus, and decreased the level of interleukin-1β (IL-1β) in the plasma, prefrontal cortex, and hippocampus at 1 week postoperatively. In addition, DSP-4 treatment attenuated hippocampal-dependent learning and memory impairment in rats with POCD, with a downregulation of the activation of microglia and astrocytes in the prefrontal cortex and hippocampus. In conclusion, these findings provide evidence of the effects of LCNE in modulating neuroinflammation in rats with POCD and provide a new perspective in the prevention and treatment of POCD.
format	article
author	Jiayu Wang Ying Zhou Ke Li Xiaofeng Li Meimei Guo Mian Peng
author_facet	Jiayu Wang Ying Zhou Ke Li Xiaofeng Li Meimei Guo Mian Peng
author_sort	Jiayu Wang
title	A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation
title_short	A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation
title_full	A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation
title_fullStr	A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation
title_full_unstemmed	A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation
title_sort	noradrenergic lesion attenuates surgery-induced cognitive impairment in rats by suppressing neuroinflammation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1ce45f12aa6548cfa974cf54a36a56d9
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A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

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