Curcumin ameliorates memory deficits via neuronal nitric oxide synthase in aged mice

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 (50 mg/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.