Fast green FCF prevents postoperative cognitive dysfunction via the downregulation of the P2X4 receptor in mice

作者全名："Liu, Jun; Gao, Tao; Zhou, Bin; Xu, Xiaoxiao; Zhai, Xiaojie; Yao, Qinghuan; Chen, Xiaowei; Liu, Lin; Cui, Wei; Wu, Xiang"

作者地址："[Liu, Jun; Zhou, Bin; Xu, Xiaoxiao; Zhai, Xiaojie; Yao, Qinghuan; Cui, Wei; Wu, Xiang] Ningbo Univ, Affiliated Hosp 1, Ningbo 315010, Peoples R China; [Gao, Tao] Chongqing Med Univ, Univ Town Hosp, Chongqing 401331, Peoples R China; [Chen, Xiaowei; Cui, Wei] Ningbo Univ, Translat Med Ctr Pain Emot & Cognit, Sch Med, Zhejiang Prov Key Lab Pathophysiol, Ningbo 315211, Peoples R China; [Liu, Lin] Ningbo Women & Childrens Hosp, Ningbo 315012, Peoples R China; [Cui, Wei] Ningbo Kangning Hosp, Ningbo 315211, Peoples R China"

通信作者："Wu, X (通讯作者)，Ningbo Univ, Affiliated Hosp 1, Ningbo 315010, Peoples R China."

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001027791900001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：121

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Fast green FCF; Postoperative cognitive dysfunction; Neuroinflammation; NF-& kappa;B

摘要："Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms underlying POCD have not yet been clarified. The overexpression of the P2X4 receptor in the central nervous system (CNS) was reported to be associated with the onset of POCD. Fast green FCF (FGF), a widely used food dye, could decrease the expression of the P2X4 receptor in the CNS. This study aimed to explore whether FGF could prevent POCD via the down-regulation of CNS P2X4 receptor. Exploratory laparotomy under the anesthesia of fentanyl and droperidol was carried to establish an animal model of POCD in 10-12-months-olds mice. FGF significantly attenuated cognitive impairments and down-regulated the expression of the P2X4 receptor induced by surgery in mice. Moreover, the blockade of CNS P2X4 receptor by intrahippocampal injection of 5-BDBD induced cognitive-enhancing effects on POCD mice. In addition, the effects of FGF were abolished by ivermectin, which is a positive allosteric modulator of the P2X4 receptor. FGF also inhibited M1 polarization of microglia cells, decreased the phosphorylation of nuclear factor?B (NF-?B), and reduced the production of pro-inflammatory cytokines. These results suggested that FGF produced anti-POCD cognitive-enhancing effects via down-regulation of the P2X4 receptor-associated neuroinflammation, providing a support that FGF might be a potential treatment for POCD."

基金机构：Medical and Health Research project of Zhejiang Province [2021KY1043]; Ningbo Natural Science Foundation [202003 N4247]; Ningbo Public Service Technology Foundation [2022S031]

基金资助正文："Fundings This study was supported by Medical and Health Research project of Zhejiang Province (2021KY1043) , Ningbo Natural Science Foundation (202003 N4247) , and Ningbo Public Service Technology Foundation (2022S031) ."