Sildenafil ameliorates cognitive deficits and tau pathology in a senescence-accelerated mouse model
Bibliographic
The aim of this study was to explore whether sildenafil could reverse the memory impairments shown by SAMP8 mice as well as the underlying mechanisms.Sildenafil administration (7.5 mg/kg for 4 weeks) to 5-month-old SAMP8 mice attenuated spatial learning and memory impairments shown by these mice in the Morris Water Maze. Tau hyperphosphorylation (AT8 but not PHF-1 epitope) shown by SAMP8 mice at this age was also decreased in the hippocampus of sildenafil-treated mice, an effect probably related to a decrease in cyclin-dependent kinase 5 protein expression and activity (p25/p35 ratio). Sildenafil treatment was associated with phosphosphorylated Akt, which was associated with an increase of glycogen synthase kinase-3 phosphorylation, providing a plausible explanation for the reductions in tau hyperphosphorylation and attenuation of cognitive deficits shown by 9-month-old SAMP8 mice. Overall, sildenafil might be beneficial in age-related brain dysfunction and could be an emerging candidate for the treatment of other neurodegenerative diseases.