神经解剖学杂志2024,Vol.40Issue(4) :435-442.DOI:10.16557/j.cnki.1000-7547.2024.04.005

膀胱炎致小鼠焦虑模型诱导前扣带回皮质单细胞基因表达差异

Differential single-cell gene expression in the anterior cingulate cortex of mice induced by a cystitis-driven anxiety model

程果 周永生 冷冬妮 宋博
神经解剖学杂志2024,Vol.40Issue(4) :435-442.DOI:10.16557/j.cnki.1000-7547.2024.04.005

膀胱炎致小鼠焦虑模型诱导前扣带回皮质单细胞基因表达差异

Differential single-cell gene expression in the anterior cingulate cortex of mice induced by a cystitis-driven anxiety model

程果 1周永生 2冷冬妮 3宋博1
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作者信息

  • 1. 东部战区空军医院心胸泌尿外科,南京 210002
  • 2. 东部战区空军医院心胸泌尿外科,南京 210002;空军军医大学基础医学院神经生物学教研室,西安 710032
  • 3. 东部战区空军医院病理科,南京 210002
  • 折叠

摘要

目的:本研究旨在通过构建小鼠膀胱炎模型,探讨膀胱炎引发的焦虑样行为及其在前扣带回皮质(ACC)的神经生物学机制.方法:采用脂多糖(LPS)建立膀胱炎模型,通过旷场实验探究小鼠焦虑样行为,利用单细胞RNA测序技术分析ACC中的神经元基因表达改变.结果:HE染色结果提示LPS处理的小鼠膀胱存在大量炎症细胞浸润、组织水肿以及膀胱上皮脱落等炎症反应.旷场实验提示小鼠在旷场中心区域活动时间以及距离明显减少,存在明显的焦虑样行为.单细胞RNA测序质控提示数据质量较好,通过前2000个高变基因降维聚类揭示了ACC存在7群不同的细胞亚群以及5种主要的细胞类型.神经元进一步降维聚类成5群不同的细胞亚群,并鉴定出2种主要的细胞类型,差异基因分析提示神经元存在明显的基因表达改变,并且功能富集于突触功能异常等通路.结论:膀胱炎可引发ACC中特定细胞亚群的基因表达改变,提示特定的神经元类型可能在膀胱炎引发的焦虑样行为中发挥重要作用.这为深入理解膀胱炎与焦虑行为的关系提供了新的视角,为未来探究膀胱炎诱发的焦虑行为的脑区及分子机制提供了重要的实验依据.

Abstract

Objective:This study aims to investigate the anxiety-like behavior induced by cystitis and its neurobio-logical mechanisms in the anterior cingulate cortex(ACC)by constructing a mouse model of cystitis.Methods:A cys-titis model was established using lipopolysaccharide(LPS).Anxiety-like behavior in mice was explored through the open field test,and single-nucleus RNA sequencing was used to analyze changes in gene expression of neurons in the ACC.Results:HE staining results indicated significant inflammatory responses in the bladders of LPS-treated mice,including extensive infiltration of inflammatory cells,tissue edema,and bladder epithelial shedding.The open field test showed that the time and distance of mice moving in the central area of the open field were significantly reduced,indica-ting obvious anxiety-like behavior.Quality control of single-nucleus sequencing data suggested good data quality.Di-mensionality reduction clustering of the top 2000 highly variable genes revealed seven different cell subpopulations in the ACC.Five major cell types were identified in the ACC,and neurons were further clustered into five different subpopula-tions,identifying two main cell types.Differential gene analysis indicated significant changes in gene expression in neu-rons,with functional enrichment in pathways related to synaptic dysfunction.Conclusion:Cystitis can induce changes in gene expression in specific cell subpopulations in the ACC,suggesting that neurons may play an important role in the anxiety-like behavior induced by cystitis.This provides a new perspective for understanding the relationship between cystitis and anxiety behavior and offers important experimental evidence for future exploration of the brain regions and molecular mechanisms underlying cystitis-induced anxiety behavior.

关键词

膀胱炎/焦虑样行为/前扣带回皮质/单细胞RNA测序/小鼠

Key words

cystitis/anxiety/anterior cingulate cortex(ACC)/single-nucleus RNA-sequencing/mouse

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基金项目

国家卫生健康委医药卫生科技发展研究项目(WKZX2023JG0227)

东部战区空军医院院课题(22YY005)

出版年

2024
神经解剖学杂志
中国解剖学会,第四军医大学

神经解剖学杂志

CSTPCDCSCD北大核心
影响因子:0.538
ISSN:1000-7547
参考文献量20
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