Human umbilical cord-derived mesenchymal stem cells alleviate schizophrenia-relevant behaviors in amphetamine-sensitized mice by inhibiting neuroinflammation

Author:

You Min-Jung,Bang Minji,Park Hyun-Sun,Yang Bohyun,Jang Kyu Beom,Yoo Jongman,Hwang Dong-Youn,Kim MinYoung,Kim Borah,Lee Sang-Hyuk,Kwon Min-SooORCID

Abstract

AbstractAt present, therapeutic options available for treating schizophrenia are limited to monoamine-based antipsychotic drugs. Recent genome wide association study (GWAS) indicated a close relationship between immune system and schizophrenia. To leverage the GWAS finding for therapeutic strategy, we conducted a mechanism and effect study on application of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with potent immune-modulatory effect in an animal model useful for the study of schizophrenia. Schizophrenia-relevant behaviors were induced by amphetamine administration (amphetamine-sensitized mice) and the effect of a single intravenous administration of hUC-MSC was examined in the amphetamine-sensitized mice. Schizophrenia-relevant behaviors were assessed by open field test, light/dark box, social interaction test, latent inhibition, prepulse inhibition, tail suspension test, and forced swimming test. Our results indicated that neuroinflammation along with peripheral TNF-α elevation is associated with schizophrenia-relevant behaviors in amphetamine-sensitized mice. In addition, hUC-MSC inhibited schizophrenia-relevant and the neuroinflammatory changes. The main mechanism of hUC-MSC was associated with the induction of Treg and production of the anti-inflammatory cytokine, IL-10 in periphery. In vitro study revealed that amphetamine did not directly induce a neuroinflammatory reaction, while recombinant TNF-α (rTNF-α) increased mRNA expression of TNF-α, KMO, and IL-1β in several microglial cell lines. Moreover, recombinant IL-10 (rIL-10) and MSC conditioned media inhibited the inflammatory response in rTNF-α-treated microglial cells. Assuming that hUC-MSCs rarely reach the CNS and do not remain in the body for an extended time, these findings suggest that a single hUC-MSC infusion have long-term beneficial effect via regulatory T cell induction and secretion of IL-10 in amphetamine-sensitized mice.

Publisher

Springer Science and Business Media LLC

Subject

Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3