Key Laboratory of Longevity and Aging-Related Disease of Chinese Ministry of Education, Center for Translational Medicine and School of Preclinical Medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China.
School of International Education, Guangxi Medical University, Nanning, 530021, Guangxi, China.
Neuromolecular Med. 2024 Oct 29;26(1):42. doi: 10.1007/s12017-024-08811-3.
Cognitive dysfunction has been accepted as a possible complication of type 2 diabetes (T2D), but few studies revealed the potential roles of Long non‑coding RNAs (lncRNAs) in cognitive dysfunction in T2D. The current research aims to demonstrate the specific expression patterns of lncRNA-mRNA in the hippocampi of T2D db/db mice exhibiting cognitive impairment. In this study, the results from behavioral tests showed that T2D db/db mice displayed short-term and spatial working memory deficits compared to db/m mice. Furthermore, western blot analysis demonstrated that compared with db/m mice, p-GSK3β (ser9) protein levels were markedly elevated in T2D db/db mice (P < 0.01). In addition, though not statistically significant, the ratio of p-Tau (Ser396) to Tau 46, α-Synuclein expression, and p-GSK3α (ser21) expression were also relatively higher in T2D db/db mice than in db/m mice. The microarray profiling revealed that 75 lncRNAs and 26 mRNAs were dysregulated in T2D db/db mice (> 2.0 fold change, P < 0.05). GO analysis demonstrated that the differentially expressed mRNAs participated in immune response, extracellular membrane-bounded organelle, and extracellular region. KEGG analysis revealed that the differentially expressed mRNAs were mainly involved in one carbon pool by folate, glyoxylate and dicarboxylate metabolism, autophagy, glycine, serine and threonine metabolism, and B cell receptor signaling pathway. A lncRNA‑mRNA coexpression network containing 71 lncRNAs and 26 mRNAs was built to investigate the interaction between lncRNA and mRNA. Collectively, these results revealed the differential hippocampal expression profiles of lncRNAs in T2D mice with cognitive dysfunction, and the findings from this study provide new clues for exploring the potential roles of lncRNAs in the pathogenesis of cognitive dysfunction in T2D.
认知功能障碍已被认为是 2 型糖尿病（T2D）的一种可能并发症，但很少有研究表明长链非编码 RNA（lncRNA）在 T2D 认知功能障碍中的潜在作用。目前的研究旨在展示在表现出认知障碍的 T2D db/db 小鼠海马中 lncRNA-mRNA 的特定表达模式。在这项研究中，行为测试的结果表明，与 db/m 小鼠相比，T2D db/db 小鼠表现出短期和空间工作记忆缺陷。此外，Western blot 分析表明，与 db/m 小鼠相比，T2D db/db 小鼠中 p-GSK3β（ser9）蛋白水平显著升高（P<0.01）。此外，尽管没有统计学意义，但 T2D db/db 小鼠中 p-Tau（Ser396）与 Tau 46、α-Synuclein 表达和 p-GSK3α（ser21）表达的比值也相对高于 db/m 小鼠。微阵列分析显示，在 T2D db/db 小鼠中，75 个 lncRNA 和 26 个 mRNA 失调（>2.0 倍变化，P<0.05）。GO 分析表明，差异表达的 mRNAs 参与免疫反应、细胞外膜结合细胞器和细胞外区域。KEGG 分析表明，差异表达的 mRNAs 主要参与叶酸、乙醛酸盐和二羧酸代谢、自噬、甘氨酸、丝氨酸和苏氨酸代谢以及 B 细胞受体信号通路的一碳池。构建了一个包含 71 个 lncRNA 和 26 个 mRNA 的 lncRNA-mRNA 共表达网络，以研究 lncRNA 与 mRNA 之间的相互作用。综上所述，这些结果揭示了认知功能障碍的 T2D 小鼠海马中 lncRNA 的差异表达谱，本研究的结果为探索 lncRNA 在 T2D 认知功能障碍发病机制中的潜在作用提供了新的线索。
