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

作者：Chenliang Zhou, Bo Peng, Zhenghui Qin, Wei Zhu, Cuiping Guo · 发表于：BMC Neuroscience · 年份：2021 · DOI：10.1186/s12868-021-00678-5 · 被引用次数：32 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、NF-κB Signaling Pathways、Neuroscience and Neuropharmacology Research

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 adminis...