Experimental study on the action mechanism of NMDAR in diabetic mice with cognitive dysfunction

doi:10.3969/j.issn.1002-7386.2018.01.009

Abstract：Objective To observe the changes of the expression levels of N-methyl-D-aspartate receptor (NMDAR) mRNA in hippocampus of db/db mice,and to explore its action mechanism in pathogenesis of cognitive dysfunction in diabetic mice.Methods Eight male C57BL/KsJ-db/db mice were selected as diabetes group,and the other 10 C57BL/KsJ-db/m mice were selected as control group.After 6-week feeding,the levels of blood glucose and body weight were measured,moreover,the learning and memory ability of mice in both groups were detected by Morris water maze test,and the changes of long-term potentiation (LTP) in hippocampus were observed by using neuro-electrophysiological technique,meanwhile,the expression levels of NMDAR2B mRNA in hippocampus CA1 area were detected by Real-Time PCR.Results The levels of blood glucose and body weight in diabetes group were significantly higher than those in control group (P ＜ 0.05).The results by Morris water maze test showed that the escaping latent time (s) was prolonged,and the average number of times of crossing platform exploration was obviously decreased in diabetes group,as compared with that in control group (P ＜ 0.05).The electrophysiological experiment showed that the increased amplitude of PS was observed in both groups after high frequency stimulation,moreover,the average PS amplitude in diabetes group was significantly lower than that in control group (136.17 ± 12.73 ％ vs 251.67±43.78 ％,P ＜0.05).Real-Time PCR showed that the expression levels of NMDAR2B mRNA were (1.86 ± 0.14) and (1.02 ± 0.12),respectively in control group and in diabetes group,which in diabetes group were significantly lower than those in control group (P ＜ 0.05).Conclusion The db/db mice may develop a significant decrease in learning and memory ability,and the low expression of NMDAR may be one of mechanisms of diabetic cognitive deficits.