Abstract:

[Abstract] Objective  To investigate the impact and mechanism of insulin on learning and memory of Alzheimer (AD)-like mice induced by streptozotocin (STZ) intracerebroventricular (i.c.v.) injection. Methods  Twenty-one mice were randomly divided into three groups, seven mice in each group: control group (CON), the model group (STZ) and insulin (INS) treatment group. STZ i.c.v. injection was used to establish AD mouse model in the latter two groups. The subcutaneous injection of insulin was administered for 30 days to INS group. Morris water maze was applied to detect the learning and memory ability of mice and Western blotting to analyze the levels of phosphorylated Tau and neurofilament (NFs) proteins. Fluoro-Jade B (FJB) was used to label the degenerative neurons. Results  Compared with CON group, the escape latency and path length were increased in STZ group (P < 0.05) with fewer number of crossing hidden platform than that of CON group (P < 0.05). The phosphorylation levels in sites of Ser199/202, Ser396/404, Thr212 and Thr205 of Tau protein and NFs protein phosphorylation were increased in STZ group compared with those of CON group (P < 0.05). The number of FJB-positive neurons was much more in STZ group than that in CON group (P < 0.001). Ccompared with STZ group, the learning and memory were improved, the escape latency and path length were decreased in INS group (P < 0.05). There was a larger number of crossing hidden platform in INS group than that of STZ group (P < 0.05). The phosphorylation levels of Tau in different sites and NFs protein phosphorylation were significantly decreased in INS group than those of STZ group (P < 0.05). The mean integrated optical density of FJB-positive neurons was much fewer in mouse hippocampus in INS group than that of STZ group (P < 0.001). Conclusion Insulin could protect learning and memory function of AD-like mice induced by STZ i.c.v. injection, which may be related to the decrease of the hyperphosphorylation of Tau and NFs proteins, and may be related to the reduction of the neural degeneration.

Key words: Insulin, Alzheimer disease, streptozotocin, tau, neurofilaments, Morris water maze