and Protect Against Decreased KCC2 Expression Induced by the Lipopolysaccharide Treatment in PC-12 Cells and Improve Behavioral Abnormalities in Male Mice

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Dec 13

PMID 38090003

Authors

Kazuo Tomita

Yukiko Oohara

Kento Igarashi

Junichi Kitanaka

Nobue Kitanaka

Koh-Ichi Tanaka

Mehryar Habibi Roudkenar

Amaneh Mohammadi Roushandeh

Mitsutaka Sugimura

Tomoaki Sato

Affiliations

Soon will be listed here.

Abstract

(KSS) and (KKT) have been traditionally prescribed for neuropsychiatric symptoms in Japan. However, the molecular mechanism of its effect is not elucidated enough. On the other hand, it has been reported that lipopolysaccharide derived from ( LPS) is involved not only in periodontal disease but also in the systemic diseases such as psychiatric disorders via neuroinflammation. Here, we investigated the molecular mechanism of KSS and KKT treatment by LPS-induced neuropathy using PC-12 cells. When LPS was administrated during the NGF treatment, the KCC2 expression was decreased in PC-12 cells. LPS treatment also decreased the WNK and phospho SPAK (pSPAK) expression and enhanced GSK-3β expression that negatively regulates WNK-SPAK signaling. Moreover, when KSS or KKT was administrated before LPS treatment, the decrease of KCC2, WNK and pSPAK was rescued. KSS and KKT treatment also rescued the enhancement of GSK3β expression by LPS treatment. Furthermore, KSS, KKT and/or oxytocin could rescue behavioral abnormalities caused by LPS treatment by animal experiments. These effects were not shown in the Goreisan treatment, which has been reported to act on the central nervous system. These results indicate that KSS and KKT are candidates for therapeutic agents for neural dysfunction.

Citing Articles

Therapeutic potential for KCC2-targeted neurological diseases.

Tomita K, Kuwahara Y, Igarashi K, Kitanaka J, Kitanaka N, Takashi Y Jpn Dent Sci Rev. 2023; 59:431-438.

PMID: 38022385 PMC: 10665825. DOI: 10.1016/j.jdsr.2023.11.001.

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