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Cilostazol, a phosphodiesterase 3 inhibitor, as a potential therapeutic target for the treatment of dementia.

[Speaker] Yanai, Shuichi:1
[Co-author] Kojima, Kai:1, Arasaki, Tomoko:1, Endo, Shogo:1
1:Tokyo Metropolitan Institute of Gerontology (Japan)

cAMP signaling pathway is involved in variety of functions including learning and memory. Intracellular cAMP is hydrolyzed by phosphodiesterases (PDEs), therefore, PDE inhibitors elevate intracellular cAMP concentration to enhance its physiological functions. In the present study, we examined the effects of long-term administration of cilostazol, a PDE3 selective inhibitor, on age-related learning and memory decline in 8-month old senescence accelerated mouse prone 8 (SAMP8).
In the Pavlovian fear conditioning task, 1.5% cilostazol-administered SAMP8 showed significantly higher conditioned freezing than non-cilostazol-administered SAMP8 in both cue- and context-dependent memory tests. In addition, cilostazol significantly increased the number of phospholylated-CREB positive cells in the hippocampal dentate gyrus. Long-term administration of cilostazol may exert its beneficial effects on learning and memory by enhancing the cAMP signaling pathway in the hippocampus. The results obtained from the present study may lead cilostazol to direct attention to cilostazol as a potential therapeutic target for age-related memory decline.
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