| First Author | Palmeri A | Year | 2013 |
| Journal | Behav Brain Res | Volume | 240 |
| Pages | 11-20 | PubMed ID | 23174209 |
| Mgi Jnum | J:197073 | Mgi Id | MGI:5490722 |
| Doi | 10.1016/j.bbr.2012.10.060 | Citation | Palmeri A, et al. (2013) Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory. Behav Brain Res 240:11-20 |
| abstractText | Aging is characterized by a progressive cognitive decline that leads to memory impairment. Because the cyclic nucleotide cascade is essential for the integrity of synaptic function and memory, and it is down-regulated during aging and in neurodegenerative disorders, we investigated whether an increase in cGMP levels might rescue age-related synaptic and memory deficits in mice. We demonstrated that acute perfusion with the phosphodiesterase-5 inhibitor sildenafil (50 nM) ameliorated long-term potentiation in hippocampal slices from 26-30-month-old mice. Moreover, chronic intraperitoneal injection of sildenafil (3mg/kg for 3 weeks) improved age-related spatial learning and reference memory as tested by the Morris Water Maze, and recognition memory as tested by the Object Recognition Test. Finally, sildenafil restored central cAMP responsive element-binding protein (CREB) phosphorylation, which is crucial for synaptic plasticity and memory. Our data suggest that inhibition of phosphodiesterase-5 may be beneficial to treat age-related cognitive dysfunction in a physiological mouse model of aging. |
