Effects Of Streptozotocin And Alloxan Intraventricular Injection On The Learning And Memory Abilities Of Mice And The Mechanisms

Objective:Explore on the effects of streptozotocin and alloxan intracerebroventricular injection on learning and memory abilities of mice and the mechanisms.Methods:Intracerebrovenrticular injection of streptozotocin and alloxan was applied to investigate the mechanisms of Alzheimer’s disease-like impairment of learning and memory abilities in mice. Morris water maze was used to detect the learning and memory abilities of mice. Biochemistry and ELISA methods were used to detect the content of malonaldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and acetylcholine (Ach) and acetylcholinesterase (AchE). Western-blot and immunohistochemistry were used to analyze the alterations of phosphorylation and O-Glycosylation of neurofilaments in mice brain induced by alloxan and in AD brain.Results:The swimming time and distance to find the platform in the located navigation test were increased in the mice treated with streptozotocin compared to the control. The number of throughing the hidden platform in spatial probe test was reduced in the streptozotocin treated mice compared to the control mice. The MDA content in the brain tissue treated with streptozotocin was obviously higher than the control, while the content of SOD and GSH displayed no obvious difference between the mice treated with and without streptozotocin. The lower level of Ach and higher activity of AchE existed in brain treated with streptozotocin compared to the control.The swimming time and distance to find the platform in the located navigation test were increased in the mice treated with alloxan compared to the control mice. The number of across the hidden platform was decreased and the initial angle of entry to water was increased in the mice of alloxan treatment. Western-blot and imunohistochemistry study displayed that phosphorylation was increased and the O-Glycosylation was reduced in cytoskletal neurofilaments, similar to the alteration of neurofilament’s modification in AD brain.Conclusion: Streptozotocin and alloxan intracerebroventricular injection can cause Alzheimer’s disease-like impairment of learning and memory in mice and early pathological change of cytoskeletal protein, which might have relation with the increased oxygen free radical products, reduced Ach content and impaired glucose metabolism.