A number of
neuroprotective effects of
curcumin have been demonstrated in recent years. However, whether
curcumin exerts any beneficial effects on age-related impaired cognition and memory has not been well characterized; nor was there any detailed data on the molecular pathways activated by
curcumin. The present study attempts to investigate the effects of
curcumin on memory decline of aged mice with a focus upon the possible contribution of the
neuronal nitric oxide synthase (nNOS)/
nitric oxide (NO) pathway in the memory amelioration effect of
curcumin. The results showed that chronic administration of
curcumin (50mg/kg, i.p., 21 days) significantly ameliorated the memory acquisition ability of aged male mice in the novel object recognition and passive avoidance tasks. Immunoblotting revealed that chronic treatment of
curcumin increased nNOS expression in the prefrontal cortex, amygdala and hippocampus, as well as the enhancement of nNOS activity and NO concentration. This enhancement was suppressed by pre-treatment with
7-nitroindazole (7-NI), a specific inhibitor of
neuronal nitric oxide synthase (nNOS). Furthermore, inhibition of nNOS synthase by 7-NI also prevented the memory improvement effects of
curcumin in aged mice. Taken together, the results of the present study suggest that the amelioration of
memory deficits by
curcumin in aged mice was mediated, at least in part, by activating the nNOS activity in specific brain regions. These findings reveal the therapeutic potential of
curcumin as a preventive agent upon the deterioration of cognitive faculties.