| First Author | Orejana L | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 3 | Pages | 625.e11-20 |
| PubMed ID | 21546125 | Mgi Jnum | J:188208 |
| Mgi Id | MGI:5439695 | Doi | 10.1016/j.neurobiolaging.2011.03.018 |
| Citation | Orejana L, et al. (2012) Sildenafil ameliorates cognitive deficits and tau pathology in a senescence-accelerated mouse model. Neurobiol Aging 33(3):625.e11-20 |
| abstractText | Aging is associated with a deterioration of cognitive performance and with increased risk of neurodegenerative disorders. In the present study we tested whether the specific phosphodiesterase 5 inhibitor sildenafil could ameliorate the age-dependent cognitive impairments shown by the senescence-accelerated mouse prone-8 (SAMP8). 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). Interestingly, sildenafil also phosphorylated Akt, which was associated with an increase of glycogen synthase kinase-3beta phosphorylation, providing a plausible explanation for the reductions in tau hyperphosphorylation (AT8 and PHF-1 epitopes) 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. |
