Linc-FOXD3 knockdown enhances hippocampal NSCs activation through upregulation of the Wnt/β-catenin pathway.

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.