Deng Bingying, Cheng Xiang, Li Haoming, Qin Jianbing, Tian Meiling, Jin Guohua
Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Medical School of Nantong University, Building 3, No. 19 Qixiu Road, Congchuan District, Room 325, Nantong, 226001, China.
BMC Mol Biol. 2017 Jun 6;18(1):15. doi: 10.1186/s12867-017-0091-2.
The denervated hippocampus provides a proper microenvironment for the survival and neuronal differentiation of neural progenitors. While thousands of lncRNAs were identified, only a few lncRNAs that regulate neurogenesis in the hippocampus are reported. The present study aimed to perform microarray expression profiling to identify long noncoding RNAs (lncRNAs) that might participate in the hippocampal neurogenesis, and investigate the potential roles of identified lncRNAs in the hippocampal neurogenesis.
In this study, the profiling suggested that 74 activated and 29 repressed (|log fold-change|>1.5) lncRNAs were differentially expressed between the denervated and the normal hippocampi. Furthermore, differentially expressed lncRNAs associated with neurogenesis were found. According to the tissue-specific expression profiles, and a novel lncRNA (lncRNA2393) was identified as a neural regulator in the hippocampus in this study. The expression of lncRNA2393 was activated in the denervated hippocampus. FISH showed lncRNA2393 specially existed in the subgranular zone of the dentate gyrus in the hippocampus and in the cytoplasm of neural stem cells (NSCs). The knockdown of lncRNA2393 depletes the EdU-positive NSCs. Besides, the increased expression of lncRNA2393 was found to be triggered by the change in the microenvironment.
We concluded that expression changes of lncRNAs exists in the microenvironment of denervated hippocampus, of which promotes hippocampal neurogenesis. The identified lncRNA lncRNA2393 expressed in neural stem cells, located in the subgranular zone of the dentate gyrus, which can promote NSCs proliferation in vitro. Therefore, the question is exactly which part of the denervated hippocampus induced the expression of lncRNA2393. Further studies should aim to explore the exact molecular mechanism behind the expression of lncRNA2393 in the hippocampus, to lay the foundation for the clinical application of NSCs in treating diseases of the central nervous system.
去神经支配的海马体为神经祖细胞的存活和神经元分化提供了适宜的微环境。虽然已鉴定出数千种长链非编码RNA（lncRNA），但仅有少数调控海马体神经发生的lncRNA被报道。本研究旨在通过微阵列表达谱分析来鉴定可能参与海马体神经发生的长链非编码RNA（lncRNA），并研究已鉴定的lncRNA在海马体神经发生中的潜在作用。
在本研究中，分析结果表明，去神经支配的海马体与正常海马体之间有74种激活的lncRNA和29种抑制的lncRNA（|log倍数变化|>1.5）差异表达。此外，还发现了与神经发生相关的差异表达lncRNA。根据组织特异性表达谱，本研究鉴定出一种新的lncRNA（lncRNA2393）作为海马体中的神经调节因子。lncRNA2393在去神经支配的海马体中表达被激活。荧光原位杂交显示lncRNA2393特异性存在于海马齿状回的颗粒下区和神经干细胞（NSC）的细胞质中。lncRNA2393的敲低使5-乙炔基-2'-脱氧尿苷（EdU）阳性NSC数量减少。此外，发现lncRNA2393表达增加是由微环境变化触发的。
我们得出结论，lncRNA的表达变化存在于去神经支配的海马体微环境中，其促进海马体神经发生。已鉴定的lncRNA lncRNA2393在神经干细胞中表达，位于齿状回的颗粒下区，可促进体外NSC增殖。因此，确切的问题是去神经支配的海马体的哪一部分诱导了lncRNA2393的表达。进一步的研究应旨在探索lncRNA2393在海马体中表达背后的确切分子机制，为NSC在治疗中枢神经系统疾病中的临床应用奠定基础。
