Figure 6.

Diagram of signalling pathways indicating the possible mechanism by which sildenafil reverses the memory deficits in aged transgenic Tg2576 mice. Sildenafil increases cGMP formation by inhibiting PDE5, which can activate the pCREB pathway and its downstream gene target BDNF, which consequently mediates Arc induction. The activation of the pAkt pathway by sildenafil, and the inactivation of p25/CDK5 could have contributed to the overall effects in the memory reinstatement by decreasing phosphorylated tau in the Tg2576 mice hippocampus.