RRC ID 69054
Author Tomita K, Yamanishi-Taira S, Igarashi K, Oogai Y, Kuwahara Y, Roudkenar MH, Roushandeh AM, Miyawaki S, Kurimasa A, Sato T.
Title Oxytocin ameliorates KCC2 decrease induced by oral bacteria-derived LPS that affect rat primary cultured cells and PC-12 cells.
Journal Peptides
Abstract Inflammation, especially neuroinflammation, which is caused by stress, leads to central nervous system (CNS) dysfunction. Because lipopolysaccharides (LPSs) cause neuroinflammation, we investigated the effect of LPSs to CNS. In PC-12 cells, LPSs derived from oral bacteria reduced the expression of KCC2, a Cl- transporter. LPS derived from P. gingivalis (P. g) administered to rat primary cultured cells also reduced the KCC2 expression. However, LPSs derived from E. coli did not reduce the KCC2 expression. LPS treatment activated TLR4, IL-1β, and REST gene expressions, which led to KCC2 inactivation in PC-12 cells. The mechanism of KCC2 has been shown to play an important role in brain maturation, function (such as the GABA switch), and behavioral problems, we investigated the GABA function. We found that the GABA function was changed from inhibitory to excitatory by the LPS derived from P. g treatment. We demonstrated that the GSK3β also involved in the KCC2 reduction by LPS treatment. We show that oxytocin rescued the reduction in KCC2 expression caused by LPSs by inhibiting GSK3β signaling but vasopressin could not. Considered together, our results indicate that the LPSs from oral bacteria but not the LPS from E. coli increase the risk for brain disorders and oxytocin might be a candidate to overcome the abnormal behavior caused by brain disorders such as psychiatric disorders.
Volume 150
Pages 170734
Published 2022-4-1
DOI 10.1016/j.peptides.2021.170734
PII S0196-9781(21)00242-4
PMID 34974081
MeSH Animals Brain Diseases* Cells, Cultured Escherichia coli / metabolism Glycogen Synthase Kinase 3 beta / genetics Glycogen Synthase Kinase 3 beta / metabolism Humans Lipopolysaccharides / toxicity Oxytocin / metabolism Oxytocin / pharmacology PC12 Cells Rats Symporters* / genetics Symporters* / metabolism gamma-Aminobutyric Acid
IF 2.843
Human and Animal Cells PC-12(RCB0009)