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

BMC Neuroscience

Cuiping Guo¹  Chenliang Zhou¹  Wei Zhu²  Zhenghui Qin²  Bo Peng³ 

[1] Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China;Department of Critical Care Medicine, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China;Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China;

关键词: Lipopolysaccharides (LPS);    Metformin;    NF-κB;    Neuronal injury;    Cognitive impairments;   

DOI  :  10.1186/s12868-021-00678-5

来源: Springer

【 摘 要 】

BackgroundNeuroinflammatory 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.MethodsHere, 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.ResultsAltogether, 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.ConclusionThese 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.

【 授权许可】

CC BY