Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory

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• 作者：Agostino Palmeri^a ; Lucia Privitera^a ; Salvatore Giunta^b ; Carla Loreto^b ; Daniela Puzzo^a ; ^{danypuzzo@yahoo.it}
• 关键词：Aging ; Sildenafil ; Synaptic plasticity ; Memory ; CREB ; Hippocampus
• 刊名：Behavioural Brain Research
• 出版年：2013
• 出版时间：1 March, 2013
• 年：2013
• 卷：240
• 期：Complete
• 页码：11-20
• 全文大小：1322 K

文摘

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 (3 mg/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.