Department of Child Healthcare, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China; Department of Child Healthcare, Jiangsu Province People's Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing, 210006, China.
Department of Child Healthcare, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China.
Brain Res Bull. 2020 Aug;161:177-196. doi: 10.1016/j.brainresbull.2020.03.015. Epub 2020 Apr 25.
The incidence of attention deficit hyperactivity disorder (ADHD) in children is increasing. Long non-coding RNAs (lncRNAs) participate in many biological processes involved in the regulation of gene expression. Although numerous lncRNAs have been proven to be crucial in brain development and associated with its degeneration, changes in lncRNA expression profiles during ADHD progression and their possible roles remain unclear. The purpose of this study is to investigate the expression profiles of lncRNAs in hippocampus from an ADHD model in spontaneously hypertensive rats (SHRs) and in normal control Wistar Kyoto (WKY) rats. We determined the expression profiles of lncRNAs and mRNAs in SHRs and WKY rats using microarray analysis technology. Then, differentially expressed lncRNAs were confirmed by real-time polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analysis of differentially expressed mRNAs or nearby genes was used to predict the possible functions of the lncRNAs. A gene co-expression network was established to study the relationship between expression of lncRNAs and related mRNAs. A total of 267 differentially expressed lncRNAs (including 144 upregulated and 123 downregulated) and 311 differentially expressed mRNAs were identified in SHRs, compared to those in WKY rats. Subsequently, 15 lncRNAs were selected and confirmed by RT-PCR analysis. GO and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis showed that the dysregulated lncRNAs are involved in brain developmental processes and neuronal function and maintenance. Co-expression network analysis revealed the close relationship between the differentially expressed lncRNAs and mRNAs. Additionally, co-expression analysis of dysregulated lncRNAs with their downstream genes, which are reported in nervous system and regulation of learning and memory, indicated that lncRNA NONRATT0006598.2 was related to Baiap2 gene, which may participate in ADHD progress. Our findings contribute to understand the importance of lncRNAs and mRNAs in the progression of ADHD, and identify potential therapeutic targets for ADHD treatment.
儿童注意缺陷多动障碍（ADHD）的发病率正在上升。长非编码 RNA（lncRNA）参与许多生物过程，涉及基因表达的调控。虽然许多 lncRNA 已被证明在大脑发育中至关重要，并与大脑退化有关，但 ADHD 进展过程中 lncRNA 表达谱的变化及其可能的作用仍不清楚。本研究旨在研究自发性高血压大鼠（SHR）ADHD 模型和正常对照 Wistar Kyoto（WKY）大鼠海马中的 lncRNA 表达谱。我们使用微阵列分析技术确定了 SHR 和 WKY 大鼠中的 lncRNA 和 mRNA 表达谱。然后，通过实时聚合酶链反应（RT-PCR）确认差异表达的 lncRNA。差异表达的 mRNAs 或附近基因的基因本体（GO）和途径分析用于预测 lncRNA 的可能功能。建立基因共表达网络研究 lncRNA 与相关 mRNAs 表达之间的关系。与 WKY 大鼠相比，SHR 中总共鉴定出 267 个差异表达的 lncRNA（包括 144 个上调和 123 个下调）和 311 个差异表达的 mRNA。随后，通过 RT-PCR 分析选择并验证了 15 个 lncRNA。GO 和京都基因与基因组百科全书（KEGG）途径分析表明，失调的 lncRNA 参与大脑发育过程和神经元功能和维持。共表达网络分析揭示了差异表达的 lncRNA 与 mRNAs 之间的密切关系。此外，与神经系统和学习记忆调节中报道的失调 lncRNA 及其下游基因的共表达分析表明，lncRNA NONRATT0006598.2 与 Baiap2 基因有关，可能参与 ADHD 进展。我们的研究结果有助于理解 lncRNA 和 mRNAs 在 ADHD 进展中的重要性，并确定 ADHD 治疗的潜在治疗靶点。
