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.

中文翻译：

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去神经支配的海马中的微阵列表达谱鉴定出功能上参与神经发生的长的非编码RNA。

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合适的微环境。尽管鉴定了成千上万的lncRNA，但仅报道了少数调节海马神经发生的lncRNA。本研究旨在执行微阵列表达谱分析，以鉴定可能参与海马神经发生的长非编码RNA（lncRNA），并研究已鉴定的lncRNA在海马神经发生中的潜在作用。在这项研究中，该分析表明在去神经支配的海马和正常海马体中差异表达了74个激活的lncRNA（| log倍数变化|> 1.5）。此外，发现了与神经发生有关的差异表达的lncRNA。根据组织特异性表达谱，这项研究确定了一种新型的lncRNA（lncRNA2393）作为海马神经调节剂。在去神经支配的海马中，lncRNA2393的表达被激活。FISH显示lncRNA2393特别存在于海马齿状回的亚颗粒区和神经干细胞（NSC）的细胞质中。lncRNA2393的敲低消耗了EdU阳性NSC。此外，发现lncRNA2393的表达增加是由微环境的变化触发的。我们得出的结论是，失神经海马的微环境中存在lncRNAs的表达变化，其促进海马神经发生。鉴定的lncRNA lncRNA2393在齿状回的亚颗粒区的神经干细胞中表达，可以促进NSCs的体外增殖。所以，问题恰恰是失神经海马的哪一部分诱导了lncRNA2393的表达。进一步的研究应旨在探索海马中lncRNA2393表达背后的确切分子机制，为NSCs在中枢神经系统疾病的临床应用奠定基础。