中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (24): 5237-5244.doi: 10.12307/2025.723

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    下一篇

自主运动对小鼠海马分子表达特征影响:基于GEO数据库基因表达谱分析

叶  星1,2,刘仁仪2   

  1. 1北京体育大学运动人体科学学院,北京市  100084;2中国地质大学(武汉)体育学院,湖北省武汉市  430074


  • 收稿日期:2024-07-31 接受日期:2024-10-08 出版日期:2025-08-28 发布日期:2025-02-06
  • 通讯作者: 刘仁仪,博士,教授,中国地质大学(武汉)体育学院,湖北省武汉市 430074
  • 作者简介:叶星,女,1998年生,四川省成都市人,汉族,北京体育大学在读博士,主要从事运动生物化学方向的研究。
  • 基金资助:
    中央高校基本科研业务费专项资金“杰出人才培育基金”资助项目(CUG150607),项目负责人:刘仁仪

Effects of voluntary exercise on molecular expression profiles in the hippocampus of mice: a gene expression profile analysis based on the GEO database

Ye Xing1, 2, Liu Renyi2    

  1. 1School of Sports and Human Sciences, Beijing Sport University, Beijing 100084, China; 2School of Physical Education, China University of Geosciences (Wuhan), Wuhan 430074, Hubei Province, China
  • Received:2024-07-31 Accepted:2024-10-08 Online:2025-08-28 Published:2025-02-06
  • Contact: Liu Renyi, PhD, Professor, School of Physical Education, China University of Geosciences (Wuhan), Wuhan 430074, Hubei Province, China
  • About author:Ye Xing, Doctoral candidate, School of Sports and Human Sciences, Beijing Sport University, Beijing 100084, China; School of Physical Education, China University of Geosciences (Wuhan), Wuhan 430074, Hubei Province, China
  • Supported by:
    the “Outstanding Talent Cultivation Fund” of the Fundamental Research Funds for the Central Universities, No. CUG150607 (to LRY)

摘要:


文题释义:
海马体:是大脑颞叶内的重要结构,对记忆和学习至关重要。海马体参与长期记忆的编码、存储与提取,是空间导航和情绪调节的关键脑区。海马体的功能异常与多种认知障碍相关,其健康状态直接影响认知能力和行为表现。
基因:是DNA上的遗传单位,负责编码蛋白质,控制生物体的发育、功能和遗传特性。基因是生物多样性和进化的基础,对健康和疾病有深远影响。

背景:海马体对认知功能至关重要,运动有望提升认知并缓解认知衰退,然而其分子机制尚不明了。生物信息学通过分析运动对海马体分子表达的影响,从而揭示关键机制,为理解运动如何促进认知及制定干预策略提供新的视角。
目的:采用生物信息学方法深入分析自主运动干预对小鼠海马组织基因表达谱的影响,通过研究差异表达基因的生物学功能及其潜在的调控网络,揭示运动对海马体神经功能调控的分子机制。
方法:通过美国国立生物技术信息中心NCBI创建并维护的基因表达综合数据库(GEO)获取自主运动干预小鼠海马组织的基因表达微阵列数据集(GSE42904和GSE29075),随后采用R语言中的Limma和DESeq2包进行严格的差异基因分析,并借助ggplot2包绘制火山图直观展示分析结果;通过funrich软件识别共同的差异表达基因;利用R语言中的clusterProfiler包进行基因本体论和京都基因与基因组百科全书通路富集分析;通过在线分析工具STRING对差异表达基因进行蛋白-蛋白相互作用网络分析;应用Cytoscape软件进一步筛选核心靶点。
结果与结论:①在GSE42904数据集中,自主运动干预导致小鼠海马体123个基因存在差异,它们主要参与节律过程、糖基化等基因本体论生物过程,并涉白细胞介素17、钙、乙醇等多条京都基因与基因组百科全书信号通路,蛋白-蛋白相互作用网络确定的关键枢纽基因包括Npy、Mapk3、Mapk11和Chgb等;②GSE29075数据集中,自主运动引起小鼠海马455个差异基因表达,它们主要参与细胞投射组织的正调控、凋亡负调控信号等基因本体论生物过程,并在神经退行性疾病相关通路显著富集,蛋白-蛋白相互作用网络确定的关键枢纽基因包括Eed、Bptf和Nedd8等;③提示自主运动可以显著调节小鼠海马中Chrm1、Eed、Npy、Mapk3、Mapk11和Map2k1等关键基因表达,这些基因可能在神经退行性疾病、钙信号传导等生物学过程中起着核心的调控作用,自主运动可能通过影响神经发生和突触可塑性来促进认知功能。
https://orcid.org/0000-0002-6369-4105(叶星);https://orcid.org/0000-0003-4448-5719(刘仁仪)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 自主运动, 小鼠, 海马体, 差异表达基因, 信号通路, 蛋白互作网络, GEO数据库, 生物信息学

Abstract: BACKGROUND: The hippocampus is crucial for cognitive function, and exercise holds promise for enhancing cognition and alleviating cognitive decline. However, the molecular mechanisms underlying these effects remain unclear. Bioinformatics, by analyzing the impact of exercise on molecular expression in the hippocampus, helps reveal key mechanisms, providing new insights into how exercise promotes cognition and informing the development of intervention strategies.
OBJECTIVE: Using bioinformatics methods to conduct an in-depth analysis of the gene expression profiles of hippocampal tissue in mice subjected to voluntary exercise interventions and by examining the biological functions of differentially expressed genes and their potential regulatory networks to elucidate the molecular mechanisms by which exercise modulates neural function in the hippocampus.
METHODS: Gene expression microarray datasets (GSE42904 and GSE29075) from the Gene Expression Omnibus (GEO) database were obtained for hippocampal tissue in mice subjected to voluntary exercise interventions. Strict differential gene analysis was performed using the Limma and DESeq2 packages in R, and the results were visually presented using volcano plots generated by the ggplot2 package. Common differentially expressed genes were identified using the FunRich software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the clusterProfiler package in R. Protein-protein interaction networks of differentially expressed genes were analyzed using the online tool STRING, and core targets were further screened using Cytoscape software. 
RESULTS AND CONCLUSION: In the GSE42904 dataset, voluntary exercise intervention led to the differential expression of 123 genes in the hippocampus of mice, primarily involved in rhythmic processes, glycosylation, and other GO biological processes. These genes were also associated with multiple KEGG pathways, including interleukin-17, calcium, and ethanol signaling. Key hub genes identified in the protein-protein interaction network included Npy, Mapk3, Mapk11, and Chgb. In the GSE29075 dataset, voluntary exercise resulted in the differential expression of 455 genes in the hippocampus, mainly involved in the positive regulation of cellular projection organization, negative regulation of apoptotic signaling, and other GO biological processes. These genes were significantly enriched in pathways related to neurodegenerative diseases. Key hub genes identified in the protein-protein interaction network included Eed, Bptf, and Nedd8. To conclude, voluntary exercise significantly regulates the expression of key genes such as Chrm1, Eed, Npy, Mapk3, Mapk11, and Map2k1 in the hippocampus of mice. These genes play a core regulatory role in biological processes such as neurodegenerative diseases and calcium signaling. Voluntary exercise may promote cognitive function by influencing neurogenesis and synaptic plasticity.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

Key words: voluntary exercise, mouse, hippocampus, differentially expressed genes, signaling pathways, protein-protein interaction network, GEO database, bioinformatics

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