Early postnatal activation of A2ARs alleviates social deficits by attenuating the abnormal infiltration of peripheral neutrophils in the BTBR T + Itpr3 tf /J mouse model of autism

Author:

He Xie1,Zhou Mi1,Yang Teng1,Ren Jia-Kui1,Sun Li1,Liu Tian-Yao1,Sun Jian-Bin1,Ma Peng-Jiao1,Liu He-Ting1,Fang Jing-Qin1,Dai Shuang-Shuang1

Affiliation:

1. Army Medical University

Abstract

Abstract Background Previous studies have mainly focused on the immediate effect of drugs on autism spectrum disorders (ASDs) and complex heterogeneous neurodevelopmental disorders that have been proven to be involved with the chronic inflammation of the central nervous system. Our prior work has explored the positive role of activation of adenosine 2A receptors (A2ARs) in protecting adult BTBR T+ Itpr3tf/J mice against autism-related behaviour from the early postnatal period. However, the exact mechanism underlying the protection of A2ARs has not been comprehensively investigated. Methods The persistent protection of early postnatal activation of A2ARs in adult BTBR mice was detected utilizing behaviour tests. Pathological variation in the peripheral blood of autism patients was analysed by transcriptomic analysis, including MROAST and protein–protein interaction (PPI) analysis. The clues were further explored and validated by real-time (RT) PCR, western blotting, immunohistochemistry and transcriptomic analysis in the mouse cortex. The blood brain barrier of mice was identified by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Results Abnormal activation of myeloid cells, especially neutrophils, was detected in the peripheral blood of autism patients and the BTBR mouse cortex. The BBB permeability of BTBR mice was significantly increased, which may have facilitated the abnormal infiltration of neutrophils observed in the BTBR mouse cortex. Furthermore, the early postnatal activation of A2ARs effectively reverses the abnormal activation and invasion of neutrophils in the mouse cortex and might result in the significant moderation of autism-related behaviour in adult BTBR mice, followed by a decrease in chronic inflammation in the mouse cortex during the early postnatal period. Conclusions We found abnormal myeloid cells in autism patients and BTBR mice and increased infiltration of neutrophils in the mouse cortex. We concluded that the early activation of A2ARs could effectively decrease the autism-related behaviour of adult BTBR mice by reversing the abnormal activation of myeloid cells and the pathological invasion of neutrophils in the mouse cortex.

Publisher

Research Square Platform LLC

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

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