中国病理生理杂志2024，Vol.40Issue(5)：815-826,12.DOI:10.3969/j.issn.1000-4718.2024.05.006
前扣带回至伏隔核GABA能神经通路调控小鼠肠易激综合征及潜在机制研究
Effect of anterior cingulate cortex-nucleus accumbens GABAergic cir-cuit on irritable bowel syndrome in mice and its underlying mechanisms
摘要
Abstract
AIM:To investigate the effects of the γ-aminobutyric acid(GABAergic)neural pathway from the anterior cingulate cortex(ACC)to the nucleus accumbens(NAc)on the regulation of irritable bowel syndrome(IBS)and its underlying mechanisms in mice.METHODS:(1)A C57BL/6J mice model of IBS was established by using chronic acute combing stress(CACS).The mice were divided into a normal group and an IBS group(n=8).The presence of IBS-like symptoms was determined through behavioural tests,an intestinal motility test and abdominal withdrawal reflex scores.(2)Fluorescence gold(FG)retrograde tracing and immunohistochemistry were used to investigate the ACC-NAc GABAergic neural pathway and to examine the activation of GABA in the ACC in IBS mice(n=8).(3)A total of 1.5 μL of normal saline(NS),GABAA receptor antagonist bicuculline(BIC)or agonist isoguvacine hydrochloride(Isog)was ad-ministered via a preburied catheter into the NAc of mice in IBS and normal groups.The mice were randomly divided into three groups(n=8):NS group,BIC group and Isog group.IBS-like symptoms were assessed.(4)The mice were prein-jected with AAV2/9-mDlx-iCre-WPRE-pA in the ACC and AAV2/2Retro Plus-hSyn-DIO-hM3D(Gq)-eGFP-WPRE-pA in the NAc and subsequently divided into four groups(n=8):NS(intraperitoneal injection)+NS(NAc microinjection)group,NS+BIC group,clozapine N-oxide(CNO)+NS group and CNO+BIC group.The mice who received AAV2/2Retro-hSyn-DIO-hM4D(Gi)-EGFP-WPRE-pA in the NAc were randomly divided into three groups(n=8):NS+NS group,NS+BIC group and CNO+NS group.Enzyme-linked immunosorbent assay(ELISA)was employed to estimate the expression levels of histamine and 5-hydroxytryptamine(5-HT)in colon tissue,and the effects of GABAergic neural pathways from ACC to NAc on IBS were studied.RESULTS:CACS induced IBS-like symptoms in mice.The results of FG retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons of ACC could project to NAc.The injection of BIC in the NAc was found to significantly reduce anxiety-like behaviours,diarrheal symptoms and visceral hy-persensitivity in the IBS mice(P<0.05).Chemogenetic inhibition of the ACC-NAc GABAergic neurons ameliorated IBS-like symptoms in mice(P<0.05).CONCLUSION:The GABAergic pathway of ACC-NAc might be involved in the regu-lation of IBS in mice,which may be related to the release of histamine and 5-HT in colon tissue.关键词
前扣带回/伏隔核/γ-氨基丁酸/焦虑样行为/肠易激综合征/内脏超敏反应Key words
anterior cingulate cortex/nucleus accumbens/γ-aminobutyric acid/anxiety-like behaviors/irri-table bowel syndrome/visceral hypersensitivity分类
医药卫生引用本文复制引用
郭瑞晓,郭菲菲,高胜利,冯旭菲,刘华,明星,孙金秋,栾心驰,刘震宇,刘蔚毅..前扣带回至伏隔核GABA能神经通路调控小鼠肠易激综合征及潜在机制研究[J].中国病理生理杂志,2024,40(5):815-826,12.基金项目
中国博士后科研基金资助项目(No.2018M632627) （No.2018M632627）
山东省大学生创新创业训练计划项目(No.S202311065054) （No.S202311065054）
