Microarray expression profiling in the denervated hippocampus identifies long noncoding RNAs functionally involved in neurogenesis

摘要

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.