Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway

Abstract Background Neuroinflammatory response is considered to be a high-risk factor for cognitive impairments in the brain. Lipopolysaccharides (LPS) is an endotoxin that induces acute inflammatory responses in injected bodies. However, the molecular mechanisms underlying LPS-associated cognitive...

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Autores principales:	Chenliang Zhou, Bo Peng, Zhenghui Qin, Wei Zhu, Cuiping Guo
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Lipopolysaccharides (LPS) Metformin NF-κB Neuronal injury Cognitive impairments Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurophysiology and neuropsychology QP351-495
Acceso en línea:	https://doaj.org/article/32077918c22d4302b1137270a31253d8
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spelling	oai:doaj.org-article:32077918c22d4302b1137270a31253d82021-11-28T12:30:38ZMetformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway10.1186/s12868-021-00678-51471-2202https://doaj.org/article/32077918c22d4302b1137270a31253d82021-11-01T00:00:00Zhttps://doi.org/10.1186/s12868-021-00678-5https://doaj.org/toc/1471-2202Abstract Background Neuroinflammatory response is considered to be a high-risk factor for cognitive impairments in the brain. Lipopolysaccharides (LPS) is an endotoxin that induces acute inflammatory responses in injected bodies. However, the molecular mechanisms underlying LPS-associated cognitive impairments still remain unclear. Methods Here, primary hippocampal neurons were treated with LPS, and western blotting and immunofluorescence were used to investigate whether LPS induces neurons damage. At the same time, SD rats were injected with LPS (830 μg/Kg) intraperitoneally, and Open field test, Novel Objective Recognition test, Fear condition test were used to detect cognitive function. LTP was used to assess synaptic plasticity, and molecular biology technology was used to assess the NF-κB pathway, while ELISA was used to detect inflammatory factors. In addition, metformin was used to treat primary hippocampal neurons, and intraventricularly administered to SD rats. The same molecular technics, behavioral and electrophysiological tests were used to examine whether metformin could alleviate the LPS-associated neuronal damage, as well as synaptic plasticity, and behavioral alterations in SD rats. Results Altogether, neuronal damage were observed in primary hippocampal neurons after LPS intervention, which were alleviated by metformin treatment. At the same time, LPS injection in rat triggers cognitive impairment through activation of NF-κB signaling pathway, and metformin administration alleviates the LPS-induced memory dysfunction and improves synaptic plasticity. Conclusion These findings highlight a novel pathogenic mechanism of LPS-related cognitive impairments through activation of NF-κB signaling pathway, and accumulation of inflammatory mediators, which induces neuronal pathologic changes and cognitive impairments. However, metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway.Chenliang ZhouBo PengZhenghui QinWei ZhuCuiping GuoBMCarticleLipopolysaccharides (LPS)MetforminNF-κBNeuronal injuryCognitive impairmentsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurophysiology and neuropsychologyQP351-495ENBMC Neuroscience, Vol 22, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lipopolysaccharides (LPS) Metformin NF-κB Neuronal injury Cognitive impairments Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurophysiology and neuropsychology QP351-495
spellingShingle	Lipopolysaccharides (LPS) Metformin NF-κB Neuronal injury Cognitive impairments Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurophysiology and neuropsychology QP351-495 Chenliang Zhou Bo Peng Zhenghui Qin Wei Zhu Cuiping Guo Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway
description	Abstract Background Neuroinflammatory response is considered to be a high-risk factor for cognitive impairments in the brain. Lipopolysaccharides (LPS) is an endotoxin that induces acute inflammatory responses in injected bodies. However, the molecular mechanisms underlying LPS-associated cognitive impairments still remain unclear. Methods Here, primary hippocampal neurons were treated with LPS, and western blotting and immunofluorescence were used to investigate whether LPS induces neurons damage. At the same time, SD rats were injected with LPS (830 μg/Kg) intraperitoneally, and Open field test, Novel Objective Recognition test, Fear condition test were used to detect cognitive function. LTP was used to assess synaptic plasticity, and molecular biology technology was used to assess the NF-κB pathway, while ELISA was used to detect inflammatory factors. In addition, metformin was used to treat primary hippocampal neurons, and intraventricularly administered to SD rats. The same molecular technics, behavioral and electrophysiological tests were used to examine whether metformin could alleviate the LPS-associated neuronal damage, as well as synaptic plasticity, and behavioral alterations in SD rats. Results Altogether, neuronal damage were observed in primary hippocampal neurons after LPS intervention, which were alleviated by metformin treatment. At the same time, LPS injection in rat triggers cognitive impairment through activation of NF-κB signaling pathway, and metformin administration alleviates the LPS-induced memory dysfunction and improves synaptic plasticity. Conclusion These findings highlight a novel pathogenic mechanism of LPS-related cognitive impairments through activation of NF-κB signaling pathway, and accumulation of inflammatory mediators, which induces neuronal pathologic changes and cognitive impairments. However, metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway.
format	article
author	Chenliang Zhou Bo Peng Zhenghui Qin Wei Zhu Cuiping Guo
author_facet	Chenliang Zhou Bo Peng Zhenghui Qin Wei Zhu Cuiping Guo
author_sort	Chenliang Zhou
title	Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway
title_short	Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway
title_full	Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway
title_fullStr	Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway
title_full_unstemmed	Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway
title_sort	metformin attenuates lps-induced neuronal injury and cognitive impairments by blocking nf-κb pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/32077918c22d4302b1137270a31253d8
work_keys_str_mv	AT chenliangzhou metforminattenuateslpsinducedneuronalinjuryandcognitiveimpairmentsbyblockingnfkbpathway AT bopeng metforminattenuateslpsinducedneuronalinjuryandcognitiveimpairmentsbyblockingnfkbpathway AT zhenghuiqin metforminattenuateslpsinducedneuronalinjuryandcognitiveimpairmentsbyblockingnfkbpathway AT weizhu metforminattenuateslpsinducedneuronalinjuryandcognitiveimpairmentsbyblockingnfkbpathway AT cuipingguo metforminattenuateslpsinducedneuronalinjuryandcognitiveimpairmentsbyblockingnfkbpathway
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Metformin attenuates LPS-induced neuronal injury and cognitive impairments by blocking NF-κB pathway

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