Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, China.
Department of Human Anatomy, School of Basic Medical Science, Changsha Medical University, Changsha, China.
Biomed Res Int. 2019 Jan 21;2019:9642589. doi: 10.1155/2019/9642589. eCollection 2019.
Alzheimer's disease (AD), characterized by memory loss, cognitive decline, and dementia, is a progressive neurodegenerative disease. Although the long noncoding RNAs (lncRNAs) have recently been identified to play a role in the pathogenesis of AD, the specific effects of lncRNAs in AD remain unclear. In present study, we have investigated the expression profiles of lncRNAs in hippocampal of intranasal LPS-mediated Alzheimer's disease models in mice by microarray method. A total of 395 lncRNAs and 123 mRNAs was detected to express differently in AD models and controls (>2.0 folds, <0.05). The microarray expression was validated by Quantitative Real-Time-PCR (qRT-PCR). The pathway analysis showed the mRNAs that correlated with lncRNAs were involved in inflammation, apoptosis, and nervous system related pathways. The lncRNA-TFs network analysis suggested the lncRNAs were mostly regulated by HMGA2, ONECUT2, FOXO1, and CDC5L. Additionally, lncRNA-target-TFs network analysis indicated the FOXL1, CDC5L, ONECUT2, and CDX1 to be the TFs most likely to regulate the production of these lncRNAs. This is the first study to investigate lncRNAs expression pattern in intranasal LPS-mediated Alzheimer's disease model in mice. And these results may facilitate the understanding of the pathogenesis of AD targeting lncRNAs.
阿尔茨海默病(AD)以记忆力减退、认知能力下降和痴呆为特征,是一种进行性神经退行性疾病。尽管长链非编码 RNA(lncRNA)最近被发现参与 AD 的发病机制,但 lncRNA 在 AD 中的具体作用仍不清楚。在本研究中,我们通过微阵列方法研究了鼻内 LPS 介导的 AD 模型中小鼠海马中的 lncRNA 表达谱。在 AD 模型和对照组中,共检测到 395 个 lncRNA 和 123 个 mRNAs 的表达存在差异(>2.0 倍,<0.05)。微阵列表达通过定量实时 PCR(qRT-PCR)进行验证。通路分析表明,与 lncRNA 相关的 mRNAs 参与了炎症、凋亡和神经系统相关通路。lncRNA-TFs 网络分析表明,lncRNA 主要由 HMGA2、ONECUT2、FOXO1 和 CDC5L 调控。此外,lncRNA-靶-TFs 网络分析表明,FOXL1、CDC5L、ONECUT2 和 CDX1 最有可能调节这些 lncRNA 的产生。这是首次研究鼻内 LPS 介导的 AD 模型中小鼠 lncRNA 表达谱。这些结果可能有助于理解针对 lncRNA 的 AD 发病机制。