Urolithin A alleviated postoperative cognitive decline in elderly mice by indu-cing mitophagy
Objective To observe whether exogenous supplementation of urolithin A(UA)can alleviate postoperative cognitive dysfunction(POCD)in elderly mice by inducing mitophagy.Methods Fifty-six C57BL/6J elderly male mice were randomly divided into 4 groups:sham group,operation group,UA group and inhibitor group.Splenectomy was performed in the oper-ation group,UA group and inhibitor group.UA and UA+3-MA(mitophagy inhibitor)were injected intravenously into UA group and inhibitor group after operation.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels in mice hippocampus were measured by ELISA three days after operation;The levels of PTEN-induced putative kinase 1(PINK1)and parkin protein in mice hippocampus were measured by Western blot;Morris water maze test was used to detect the behavior and cognitive function of mice 3 days after operation(n=8).Results The cognitive function of the elderly mice decreased(P<0.05),the levels of PINK1 and Par-kin protein in the hippocampus decreased(P<0.05),and SOD level decreased and MDA lev-el increased(P<0.05);Compared with the operation group,the cognitive function of mice in the UA group was significantly improved(P<0.05),the levels of PINK1 and Parkin protein in the hippocampus were increased(P<0.05),and SOD level increased and MDA level de-creased(P<0.05);However,mitophagy inhibitors attenuated the protective effect of UA on cognitive function in elderly mice(P<0.05).Conclusion UA can inhibit oxidative stress in hippocampal neurons by activating mitophagy and alleviate the cognitive decline in elderly mice after operation.