Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice

Abstract Background Neuroinflammation plays an important role in the onset and progression of neurodegenerative diseases such as Alzheimer’s disease. Lipopolysaccharide (LPS, endotoxin) levels are higher in the brains of Alzheimer’s disease patients and are associated with neuroinflammation and cogn...

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Main Authors: Yi Liu, Yuyun Zhang, Xian Zheng, Tongyong Fang, Xia Yang, Xuan Luo, Anlei Guo, Kelly A. Newell, Xu-Feng Huang, Yinghua Yu
Format: Article
Language:English
Published: BMC 2018-04-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12974-018-1141-5
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spelling doaj-8ac32ec564254fd987ca5b803d523c602020-11-24T21:50:30ZengBMCJournal of Neuroinflammation1742-20942018-04-0115111510.1186/s12974-018-1141-5Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in miceYi Liu0Yuyun Zhang1Xian Zheng2Tongyong Fang3Xia Yang4Xuan Luo5Anlei Guo6Kelly A. Newell7Xu-Feng Huang8Yinghua Yu9Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical UniversityJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical UniversityJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical UniversityJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical UniversityJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical UniversityJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical UniversityJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical UniversityIllawarra Health and Medical Research Institute, School of Medicine, University of WollongongJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical UniversityJiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical UniversityAbstract Background Neuroinflammation plays an important role in the onset and progression of neurodegenerative diseases such as Alzheimer’s disease. Lipopolysaccharide (LPS, endotoxin) levels are higher in the brains of Alzheimer’s disease patients and are associated with neuroinflammation and cognitive decline, while neural cholinergic signaling controls inflammation. This study aimed to examine the efficacy of galantamine, a clinically approved cholinergic agent, in alleviating LPS-induced neuroinflammation and cognitive decline as well as the associated mechanism. Methods Mice were treated with galantamine (4 mg/kg, intraperitoneal injection) for 14 days prior to LPS exposure (intracerebroventricular injection). Cognitive tests were performed, including the Morris water maze and step-through tests. mRNA expression of the microglial marker (CD11b), astrocytic marker (GFAP), and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were examined in the hippocampus by quantitative RT-PCR. The inflammatory signaling molecule, nuclear factor-kappa B (NF-κB p65), and synapse-associated proteins (synaptophysin, SYN, and postsynaptic density protein 95, PSD-95) were examined in the hippocampus by western blotting. Furthermore, NF-κB p65 levels in microglial cells and hippocampal neurons were examined in response to LPS and galantamine. Results Galantamine treatment prevented LPS-induced deficits in spatial learning and memory as well as memory acquisition of the passive avoidance response. Galantamine decreased the expression of microglia and astrocyte markers (CD11b and GFAP), pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and NF-κB p65 in the hippocampus of LPS-exposed mice. Furthermore, galantamine ameliorated LPS-induced loss of synapse-associated proteins (SYN and PSD-95) in the hippocampus. In the in vitro study, LPS increased NF-κB p65 levels in microglia (BV-2 cells); the supernatant of LPS-stimulated microglia (Mi-sup), but not LPS, decreased the viability of hippocampal neuronal cells (HT-22 cells) and increased NF-κB p65 levels as well as expression of pro-inflammatory cytokines (IL-1β, IL-6) in HT-22 cells. Importantly, galantamine reduced the inflammatory response not only in the BV-2 microglia cell line, but also in the HT-22 hippocampal neuronal cell line. Conclusions These findings indicate that galantamine could be a promising treatment to improve endotoxin-induced cognitive decline and neuroinflammation in neurodegenerative diseases.http://link.springer.com/article/10.1186/s12974-018-1141-5GalantamineLipopolysaccharideNF-κB p65MicrogliaAstrocytes
collection DOAJ
language English
format Article
sources DOAJ
author Yi Liu
Yuyun Zhang
Xian Zheng
Tongyong Fang
Xia Yang
Xuan Luo
Anlei Guo
Kelly A. Newell
Xu-Feng Huang
Yinghua Yu
spellingShingle Yi Liu
Yuyun Zhang
Xian Zheng
Tongyong Fang
Xia Yang
Xuan Luo
Anlei Guo
Kelly A. Newell
Xu-Feng Huang
Yinghua Yu
Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice
Journal of Neuroinflammation
Galantamine
Lipopolysaccharide
NF-κB p65
Microglia
Astrocytes
author_facet Yi Liu
Yuyun Zhang
Xian Zheng
Tongyong Fang
Xia Yang
Xuan Luo
Anlei Guo
Kelly A. Newell
Xu-Feng Huang
Yinghua Yu
author_sort Yi Liu
title Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice
title_short Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice
title_full Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice
title_fullStr Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice
title_full_unstemmed Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice
title_sort galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice
publisher BMC
series Journal of Neuroinflammation
issn 1742-2094
publishDate 2018-04-01
description Abstract Background Neuroinflammation plays an important role in the onset and progression of neurodegenerative diseases such as Alzheimer’s disease. Lipopolysaccharide (LPS, endotoxin) levels are higher in the brains of Alzheimer’s disease patients and are associated with neuroinflammation and cognitive decline, while neural cholinergic signaling controls inflammation. This study aimed to examine the efficacy of galantamine, a clinically approved cholinergic agent, in alleviating LPS-induced neuroinflammation and cognitive decline as well as the associated mechanism. Methods Mice were treated with galantamine (4 mg/kg, intraperitoneal injection) for 14 days prior to LPS exposure (intracerebroventricular injection). Cognitive tests were performed, including the Morris water maze and step-through tests. mRNA expression of the microglial marker (CD11b), astrocytic marker (GFAP), and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were examined in the hippocampus by quantitative RT-PCR. The inflammatory signaling molecule, nuclear factor-kappa B (NF-κB p65), and synapse-associated proteins (synaptophysin, SYN, and postsynaptic density protein 95, PSD-95) were examined in the hippocampus by western blotting. Furthermore, NF-κB p65 levels in microglial cells and hippocampal neurons were examined in response to LPS and galantamine. Results Galantamine treatment prevented LPS-induced deficits in spatial learning and memory as well as memory acquisition of the passive avoidance response. Galantamine decreased the expression of microglia and astrocyte markers (CD11b and GFAP), pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and NF-κB p65 in the hippocampus of LPS-exposed mice. Furthermore, galantamine ameliorated LPS-induced loss of synapse-associated proteins (SYN and PSD-95) in the hippocampus. In the in vitro study, LPS increased NF-κB p65 levels in microglia (BV-2 cells); the supernatant of LPS-stimulated microglia (Mi-sup), but not LPS, decreased the viability of hippocampal neuronal cells (HT-22 cells) and increased NF-κB p65 levels as well as expression of pro-inflammatory cytokines (IL-1β, IL-6) in HT-22 cells. Importantly, galantamine reduced the inflammatory response not only in the BV-2 microglia cell line, but also in the HT-22 hippocampal neuronal cell line. Conclusions These findings indicate that galantamine could be a promising treatment to improve endotoxin-induced cognitive decline and neuroinflammation in neurodegenerative diseases.
topic Galantamine
Lipopolysaccharide
NF-κB p65
Microglia
Astrocytes
url http://link.springer.com/article/10.1186/s12974-018-1141-5
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