糖尿病合并TREM2突变相关认知功能障碍的生物信息学分析

Bioinformatics analysis of cognitive dysfunction associated with diabetes mellitus with TREM2 mutation

目的通过生物信息学分析探寻糖尿病(DM)合并髓系细胞触发受体-2(TREM2)突变相关认知功能障碍的核心基因及可能的治疗靶点。方法利用微阵列数据分析,分别得到糖尿病合并TREM2突变相关认知功能障碍2个疾病的差异基因并交集得到共同的差异基因。对其进行GO分析、KEGG和Reactome通路分析,利用在线数据库构建蛋白质-蛋白质相互作用网络(PPI);最后利用水迷宫检测糖尿病和TREM2对小鼠空间学习记忆能力的影响;利用蛋白质免疫印迹检测SNAP25表达的变化。结果在这2个数据集中,有19个基因变化相同,这些基因主要在与神经元和代谢相关的生物过程和通路富集。根据PPI分析结果,确定DNER、GFAP、GRM5、SNAP25为核心基因。Trem2敲除加重糖尿病模型小鼠空间学习记忆障碍,糖尿病小鼠海马SNAP25表达明显增加,Trem2敲除后SNAP25表达显著降低。结论本研究发现19个糖尿病合并认知功能障碍中TREM2相关基因,得到4个核心基因。这些结果为治疗糖尿病合并认知功能障碍患者提供新的实验依据。

Objective To explore the hub genes and the potential targets in the treatment of diabetes with TREM2 mutation-related cognitive dysfunction with bioinformatics analysis.Methods The cases of differential genes(DEGs)of diabetes mellitus and TREM2 mutation-related cognitive dysfunction were obtained respectively by microarray data analysis,the common differential genes were obtained by intersection between the two diseases.GO analysis,KEGG and Reactome pathway analysis were performed on the selected differential genes.The protein-protein interaction(PPI)network was constructed using online database.Finally,the effects of diabetes and TREM2 on spatial learning and memory of mice were detected by water maze,and the expression of hub gene SNAP25 was detected by Western blot.Results In both datasets,19 genes showed similar changes,mainly enriched in biological processes and pathways related to neurons and metabolism.According to PPI analysis,DNER,GFAP,GRM5 and SNAP25 were identified as hub genes.Trem2 gene knockout aggravated spatial learning and memory impairment in diabetic mice.The expression of SNAP25 in hippocampus of diabetes mice was significantly increased,and then decreased after Trem2 knockout.Conclusions This study identified 19 TREM2-related genes in diabetes with cognitive dysfunction,among which 4 hub genes were found.These results provide a new experimental basis for the treatment of diabetes patients with cognitive impairment.