Lang Haili, Xiao Renjie, Li Ying, Sun Jing, Chen Yong, Lu Yimei, Cai Junying
Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Jiangxi Medical College of Nanchang University, Nanchang, 330006, China.
Neurosci Lett. 2020 Jun 11;729:134991. doi: 10.1016/j.neulet.2020.134991. Epub 2020 Apr 22.
Hippocampal neural stem cells (H-NSCs) self-renewal and neurogenesis decrease with aging, but the intrinsic mechanism is unclear. In the current study, we detected the expression level of 8 conserved long intergenic noncoding RNAs (lincRNAs) in H-NSCs during aging, and investigated the function and mechanism of lincRNAs in regulating of H-NSCs. We found the proliferation and neuronal-differentiation capacities of H-NSCs reduced with aging and that this effect was accompanied by an increase in linc-FOXD3. Linc-FOXD3 knockdown improved H-NSCs proliferation and neuronal-differentiation capacities. Further mechanistic studies revealed that the effect of linc-FOXD3 knockdown on H-NSCs phenotypes was partially mediated by the up-regulation of Wnt/β-catenin pathway. Thus, our study provides evidence that linc-FOXD3 could be a promising therapeutic target for the recovery of H-NSCs function during aging.
海马神经干细胞（H-NSCs）的自我更新和神经发生能力会随着衰老而下降，但其内在机制尚不清楚。在本研究中，我们检测了衰老过程中H-NSCs中8种保守的长链基因间非编码RNA（lincRNAs）的表达水平，并研究了lincRNAs在调节H-NSCs中的功能和机制。我们发现，H-NSCs的增殖和神经元分化能力随着衰老而降低，并且这种效应伴随着linc-FOXD3的增加。敲低linc-FOXD3可改善H-NSCs的增殖和神经元分化能力。进一步的机制研究表明，敲低linc-FOXD3对H-NSCs表型的影响部分是由Wnt/β-连环蛋白通路的上调介导的。因此，我们的研究提供了证据表明，linc-FOXD3可能是衰老过程中恢复H-NSCs功能的一个有前景的治疗靶点。
