Analysis Of LncRNA And MRNA Expression Profiles In Brain Tissue Of AD Mice After Amyloid Polypeptide Intervention

Objective: To investigate the cognitive function,amyloid-β（Amyloid beta,Aβ）plaque changes,The expression profiles of long non-coding RNA（lncRNA）and messenger RNA（m RNA）in the brain tissue of AD mice after IAPP intervention were analyzed,in order to discover a new mechanism of IAPP intervention in AD process,which is the basis for AD The pathogenesis and prevention provide a theoretical basis.Methods: The APP/PS1 double-transgenic AD model mice were divided into the IAPP intervention group and the control group according to the random number table method,with 10 mice in each group.The IAPP intervention group was intraperitoneally injected with IAPP（concentration: 0.5 μmmol/L,dose: 200 μg/kg）,and the control group was intraperitoneally injected with the same amount of phosphate buffer.Once a day,the intervention time is 10 weeks.（1）After the intervention,the cognitive function of the mice in the two groups was detected by Morris water maze test;（2）The deposition of Aβ plaques in the hippocampus and cortex of the brain tissue of the two groups of mice was detected by immunohistochemistry;（3）The expression profiles of lncRNAs and m RNAs in the brain tissues of two groups of mice were obtained by gene chip technology,and the differentially expressed Lnc RNAs and m RNAs were screened out.Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis;（4）Combined analysis of lncRNAs subtypes（linc RNAs,Antisense lncRNAs）and m RNAs to predict the biological functions involved in differentially expressed lncRNAs and the signaling pathways involved;（5）Ce RNA network analysis showed that the potential functions of these six AD-related differentially expressed lncRNAs were closely related to dopaminergic synapses and G protein-coupling activities;（6）The quantitative real-time PCR verification was consistent with the microarray results.It was found that the differential expression of lncRNAs（AK034056 and Map3k8）in the brain tissue of the two groups of mice was the most significant.Results:（1）The results of the Morris water maze test showed that compared with the control group,the average escape latency of the mice in the IAPP intervention group was shortened,and the number of times of crossing the platform was increased（P <0.05）;The area of Aβ plaques in the hippocampus and cortex of mice was significantly lower than that in the control group（P < 0.05）;（3）The results of gene chip detection showed that compared with the control group,there were 902 differentially expressed lncRNAs in the brain tissue of the mice in the IAPP intervention group（up 238,down664）.There were 555 differentially expressed m RNAs（236 up-regulated and 319down-regulated）.（|FC| ≥ 2.0,P<0.05）.Differentially expressed m RNAs are highly enriched in G protein-coupled activity,biological process and other functions and IL-17 signaling pathway,neurodegenerative disease pathway,Alzheimer’s disease and other pathways,calcium signaling pathway,chemokine signaling pathway,phosphorylation Inositol metabolism,neuroactive ligand-receptor interaction and other pathways.（4）Combined analysis of common differences between lncRNAs subtypes and m RNAs found that a total of 780 significantly differentially expressed long intergenic lncRNAs（linc RNAs）had related coding genes（271 up-regulated,509down-regulated）.80 significantly differentially expressed antisense lncRNAs（Antisense lncRNAs）have related coding genes（38 up-regulated and 42down-regulated）.（|FC| ≥ 2.0,P<0.05）.It is predicted that the functions of lncRNAs are mainly enriched in RNA binding,catalytic activity,and cellular protein metabolism processes.access path,etc.（5）The real-time quantitative PCR verification is consistent with the chip results.It was found that the differential expression of lncRNAs（AK034056 and Map3k8）in the brain tissue of the two groups of mice was the most significant;（6）Ce RNA network analysis showed that the potential functions of these six AD-related differentially expressed lncRNA were associated with dopaminergic synapses,G protein coupling linked activities are closely related.Conclusion:（1）Intraperitoneal injection of IAPP has a protective effect on the cognitive function of AD mice;（2）Intraperitoneal injection of IAPP can reduce the deposition of Aβ plaques in the hippocampus and cortex of AD mice brain tissue;（3）Intraperitoneal injection of IAPP makes AD mice The expression profiles of lncRNA and m RNA in brain tissue changed significantly,and their functions and involved pathways were preliminarily analyzed and verified.（4）A molecular regulatory network of AD-related ce RNAs was constructed,and it was found that the potential functions of lncRNAs were closely related to dopaminergic synapses and G protein-coupling activities,which may be the potential targets of IAPP’s protective effect on AD,which is a potential target for the follow-up study of IAPP’s effect on AD.The molecular mechanism of AD treatment provides a research basis.