RRC ID 74384
Author Yamawaki Y, So H, Oue K, Asano S, Furusho H, Miyauchi M, Tanimoto K, Kanematsu T.
Title Imipramine prevents Porphyromonas gingivalis lipopolysaccharide-induced microglial neurotoxicity.
Journal Biochem Biophys Res Commun
Abstract Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobe involved in the pathogenesis of chronic periodontitis, including local inflammation of the oral cavity. However, periodontal disease has recently been identified as a significant factor in the pathogenesis of neural diseases, including Alzheimer's disease. A virulence factor, P. gingivalis-lipopolysaccharide (LPS-PG), is involved in pro-inflammatory responses, not only in peripheral tissues but also in the brain. In this study, we examined whether P. gingivalis-induced brain inflammation could be ameliorated by pharmacotherapy, using in vivo and in vitro studies. In an animal experiment, peripheral administration of LPS-PG induced inflammation in the hippocampus via microglial activation, which was inhibited by pre-treatment with the antidepressant imipramine. Similarly, LPS-PG-induced inflammation in MG-6 cells, a mouse microglial cell line, was inhibited by pre-treatment with imipramine, which caused imipramine-induced inhibition of NF-κB signaling. Culture media obtained from LPS-PG-treated MG-6 cells induced neuronal cell death in Neuro-2A cells, a mouse neuroblastoma cell line, which was prevented by pre-treatment of MG-6 cells with imipramine. These results indicate that imipramine inhibits LPS-PG-induced inflammatory responses in microglia and ameliorates periodontal disease-related neural damage.
Volume 634
Pages 92-99
Published 2022-12-17
DOI 10.1016/j.bbrc.2022.09.109
PII S0006-291X(22)01371-7
PMID 36240654
MeSH Animals Imipramine / pharmacology Inflammation / drug therapy Inflammation / metabolism Inflammation / prevention & control Lipopolysaccharides / pharmacology Mice Microglia / metabolism NF-kappa B / metabolism Periodontal Diseases* Porphyromonas gingivalis* / metabolism
IF 2.985
Human and Animal Cells MG-63(RCB1890)