Analysis of long non-coding RNA and mRNA expression profiles in brain tissue of Alzheimer's disease mice after islet amyloid polypeptide intervention
Ma Jingjing1, Li Jinping1, Hong Wenjuan1, Huang Jie1, Li Xiaoxiong1, Wang Congguo1, Hou Mingliang1, Ma Linqiu1, Fu Xiaoyan2, Qu Hongdang1, Zhou Huadong1,2
1Department of Neurology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; 2Department of Neurology, Army Characteristic Medical Center Hospital, Chongqing 400020, China
Abstract：Objective To investigate the changes of long non-coding RNA (LncRNA) and messenger RNA (mRNA) expression profiles in the brain tissue of Alzheimer's disease (AD) mice after islet amyloid polypeptide (IAPP) intervention. Methods Ten 7-month-old male APP/PS1 transgenic AD model mice were selected, weighing 20-30 g. The AD model mice were randomly divided into the IAPP intervention group and the control group according to the number table method, with 5 mice in each group. Mice in the IAPP intervention group were intraperitoneally injected with 0.5 μmol/L IAPP, 200 μg/kg, once a day. The mice in the control group were intraperitoneally injected with the same dose of phosphate buffered saline. The intervention time of the mice in both groups was 10 weeks. After the intervention, the mice were sacrificed by cervical dislocation, and total RNA was extracted from the intact brain tissue by craniotomy. The gene chip technology was used to obtain the LncRNA and mRNA expression profiles of the brain tissues of the two groups of mice, and the differentially expressed LncRNA and mRNA were screened out. Six LncRNAs were randomly selected from the differentially expressed LncRNAs and mRNAs, and real-time quantitative PCR (qRT-PCR) was used to verify the reliability of the gene chip results. The screened differentially expressed mRNAs were compared with the entries in the Gene ontology (GO) database, and the GO enrichment analysis was performed from the three fields of molecular function, biological process and cellular components; using the Kyoto encyclopedia of genes and genomes (KEGG) database Signal pathway enrichment analysis. Results During the experiment, 4 mice died, 2 mice in each group. Compared with the control group, a total of 902 LncRNAs in the IAPP intervention group had significant differences in expression, 238 were significantly up-regulated and 664 were significantly down-regulated; a total of 555 mRNAs were significantly differentially expressed, 236 were significantly up-regulated and 319 were significantly down-regulated. qRT-PCR detection verified the expression of LncRNA. Compared with the control group, the expressions of AK034056 and Spock3 in the brain tissue of the AD mice in the IAPP intervention group were up-regulated, and the expressions of Map3k8, rgs20, Rint, and Ppp2r1b were down-regulated, and the differences were statistically significant (all P values <0.05). The qRT-PCR detection results were consistent with the chip results. GO enrichment analysis: 555 differentially expressed mRNAs were enriched to obtain 2 224 GO entries. The significantly up-regulated differentially expressed mRNAs had molecular functions such as protein binding and cell cycle, were related to cellular components such as catalytic complexes and protein complexes, and participated in biological processes such as cellular metabolism and macromolecular metabolism. The significantly down-regulated differentially expressed mRNA had G protein-coupled receptor activity, transmembrane signaling receptor activity and other related molecular functions, and was related to cell adhesion complexes, integrin complexes and other cellular components; participated in G protein-coupled receptors Signaling pathways, regulation of biological processes and other biological processes. KEGG pathway enrichment analysis: 555 differentially expressed mRNAs were enriched for 62 pathways. Significantly up-regulated pathways with higher enrichment scores for differentially expressed mRNAs were neurodegenerative pathways, Alzheimer's disease pathways, oxidative phosphorylation pathways, and GABAergic synaptic pathway, etc. Significantly down-regulated pathways with higher enrichment scores for differentially expressed mRNAs were calcium signaling pathway, chemokine signaling pathway, phosphoinositide metabolism pathway, neuroactive ligand-receptor interaction pathway, interleukin-17 signaling pathway, etc. Conclusion IAPP intervention significantly changes the LncRNA and mRNA expression profiles of AD mice brain tissue. Differentially expressed mRNAs are involved in a variety of biological processes, and differentially expressed lncRNAs may exert their biological functions by regulating the expression of related mRNAs.
马晶晶, 李金平, 洪文娟, 黄洁, 李小雄, 王从过, 侯明亮, 马琳秋, 符晓艳, 屈洪党, 周华东. 胰岛淀粉样多肽对阿尔茨海默病小鼠脑组织中LncRNA和mRNA表达谱的影响[J]. 中华解剖与临床杂志, 2022, 27(5): 353-360.
Ma Jingjing, Li Jinping, Hong Wenjuan, Huang Jie, Li Xiaoxiong, Wang Congguo, Hou Mingliang, Ma Linqiu, Fu Xiaoyan, Qu Hongdang, Zhou Huadong. Analysis of long non-coding RNA and mRNA expression profiles in brain tissue of Alzheimer's disease mice after islet amyloid polypeptide intervention. Chinese Journal of Anatomy and Clinics, 2022, 27(5): 353-360.
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2022, Vol. 27 
