Analysis Of LncRNAs In Hippocampus Of P301S Mice With Alzheimer’s Disease

Background Alzheimer’s disease（AD）is one of the most common neurodegenerative disease involving a variety of nervous system dysfunctions that severely affect the lives of patients.Therefore,it is important to study the pathogenesis of AD.Long non-coding RNA（lncRNA）has long been considered as non-functional RNA.In recent years,it has been found that lncRNA also has regulatory functions,and related studies have shown that lncRNA also plays important roles in the pathogenesis of AD.P301S mice express the P301S mutant form of human microtubule-associated protein tau（MAPT）.The expression of the mutant human MAPT is five-fold higher than the expression of the endogenous mouse MAPT protein.Hyperphosphorylated,insoluble mutant human MAPT protein accumulates with age causing neurofibrillary tangles（NFTs）that affect the transport of substances,and thus show similar pathological features as humans AD.P301S mice is widely used in the study of pathophysiology,biochemistry,and histomorphology of AD,but few studies have reported the roles of lncRNA in this model.Objects Variously expressed lncRNAs and mRNAs in the hippocampus of P301 S mice and C57 mice were screened by microarray,to investigate the possible roles of lncRNAs in the development and progression of AD,and to screen out the lncRNAs related pathogenesis and treatment of AD.Materials and methods Both hippocampal tissues of P301 Smice（12 months-old,male,n=3）and C57 mice（12 months-old,male,n=3）were obtained for analysis.To identify the lncRNAs related to AD,the expression of lncRNA and mRNA was detected and the differentially expressed lncRNA and mRNA were screened.2 lncRNAs were chosed for verification of the microarray results by quantitative real-time PCR.GO and Pathway analysis of mRNA,co-expression analysis of lncRNA-mRNA,cis and trans analysis of lncRNA as also used to predict potential function of lncRNA.Results By analyzing microarray date,a total of 600 differentially expressed mRNAs were identified,of whom 417 had up-regulated expression and 183 displayed downregulated expression.And 249 differentially expressed lncRNAs were screened,of whom 124 had up-regulated expression and 125 displayed down-regulated expression.LncRNA AK037626,AK142533,NONMMUT133213.1,XR₃77567 and NONMMUT032070.2 may directly or indirectly regulate the expression of Pgap3,Pgbd1 and Phip.In addition,the trans regulatory predictions showed that lncRNA NONMMUT084550.1,AK089376,NONMMUT080626.1,AK037439,ENSMUST00000188850 were regulated by TFs of ELF2,TOPORS and IL6.Conclusions LncRNA plays important roles in the nervous system and may participate in the pathogenesis of AD through a variety of biological processes.This project has predicted possible lncRNAs that is AK037626,AK142533,NONMMUT133213.1,XR₃77567 and NONMMUT032070.2 related to AD through bioinformatics analysis methods.It provides a key basis for further revealing the roles of lncRNAs in AD.