Effect of metformin on learning and memory ability in mice during aging and the possible underlying mechanisms / 中国比较医学杂志

ABSTRACT

Objective To explore the effect of metformin on learning and memory ability and hippocampal tissue structure in mice during aging induced by D-galactose, and the possible underling mechanisms. Methods Twenty-four SPF 7-month-old female ICR mice were randomly divided into three groups. Mice of the aging group and aging+metformin group were given subcutaneous injection with D-galactose on the back to induce senescence, and given intragastric gavage with 0. 9% saline or metformin. Mice of the control group were treated with 0. 9% saline. All treatments lasted for 16 weeks. The body weight and food intake were monitored, learning and memory ability and motor function were tested by Mirros water maze and shuttle box tests, HE staining was used to observe the pathology of hippocampus in the mice, and the levels of glutathione (glutathione, GSH) in hippocampus of mice were detected by colorimetry. Results Compared with the aging group, the aging+meformin group showed diverse differencesthe body weight was decreased (P < 0. 05), the escape latency and swimming distance were decreased ( P < 0. 01 or P < 0. 05 ) , the swimming time in the target quadrant was prolonged (P < 0. 05) and swimming speed was accelerated (P < 0. 05) in the Morris water maze test. The numbers of active avoidance response were markedly increased in shuttle box test ( P < 0. 05 ) . The neurons with nuclear condensation and deep staining were obviously decreased in the dentate gyrus of hippocampus, however the GSH level was significantly increased ( P < 0. 05 ) . Conclusions Metformin can delay the decline of learning and memory ability, maintain the normal structure of hippocampus during the aging process in mice, which may be related to the reduction of body weight and enhancement of antioxidant levels in the hippocampus.