摘要
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;(2)GSE29075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。
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.
作者
叶星
刘仁仪
Ye Xing;Liu Renyi(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)
出处
《中国组织工程研究》
北大核心
2025年第24期5237-5244,共8页
Chinese Journal of Tissue Engineering Research
基金
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。
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
voluntary exercise
mouse
hippocampus
differentially expressed genes
signaling pathways
protein-protein interaction network
GEO database
bioinformatics
