Inosine improves cognitive function and decreases aging-induced oxidative stress and neuroinflammation in aged female rats

In the present study, the effect of inosine was evaluated on learning and memory of 18 months old aged female rats. Inosine (50, 100 and 200 mg/kg; i.p.) was administered to separate groups of rats for 15 successive days. Donepezil (1 mg/kg; i.p.), an acetylcholinesterase inhibitor, was used as a standard drug. Behavioral models such as Morris water maze and elevated plus maze were used to evaluate the effect of drugs on learning and memory of rats. After behavioral studies, animals were killed and their brain was isolated and further processed for estimation of various biochemical parameters such as acetylcholinesterase activity, oxidative stress markers, proinflammatory marker and histological examinations. Inosine (100 and 200 mg/kg) significantly improved learning and memory of aged rats. Further, inosine significantly reduced lipid peroxidation and nitrite, and increased the levels of reduced glutathione and superoxide dismutase. However, no significant difference in AChEs activity was observed in inosine-treated rats as compared to aged control rats. TNF-α level was found to be ameliorated in aged rats by inosine. Histopathological evaluation showed that inosine-treated aged rats have less number of pyknotic neurons in hippocampal CA1 region as compared to aged control rats. In conclusion, inosine significantly improved learning and memory of aged female rats possibly through its antioxidant as well as anti-inflammatory effect and improvement of neuronal survival in the hippocampal CA1 region. However, additional studies are required to further explore the downstream signaling pathways involved in the neuroprotective effect of inosine in aged animals.