Yhhu-3792 enhanced the self-renewal capability of NSCs in vitro and in vivo. In vitro, Yhhu-3792 increased the ratio of 5-Bromo-2-deoxyuridine+/4'-6-diamidino-2-phenylindole+ embryonic NSCs and accelerated the growth of neurospheres significantly. Yhhu-3792 activated Notch signaling pathway and promoted the expression of Notch target genes, Hes3 and Hes5. And the Notch signaling inhibitor DAPT could inhibit its function.
Yhhu-3792 act via a different mechanism with the quinazoline parent chemical group. In the eight-week-old male C57BL/6 mice, chronic Yhhu-3792 administration expanded the NSCs pool and promoted endogenous neurogenesis in the hippocampal dentate gyrus (DG). It also increased the spatial and episodic memory abilities of mice, when evaluated with the Morris water maze and Fear conditioning tests. In conclusion, Yhhu-3792 could be a novel drug candidate to promote the self-renew of NSCs and adult neurogenesis. And it may have therapeutic potential in the impairment of learning and memory associated DG dysfunction.
