The Effects And Mechanism Of Liraglutide On Learning And Memory Impairment In Sporadic AD Mice

ObjectiveResearch the effects and mechanism of liraglutide on learning and memory impairment of sporadic AD mice induced by streptozotocin (STZ) intracerebroventricular (i.c.v.) injection.MethodTwenty-four mice were randomly divided into three groups:the control group (CON), the model group (STZ) and the treatment group (LIR). STZ injection was used to establish AD mice model, and for treatment group liraglutide was administered subcutaneous for30days following STZ treatment. Morris water maze test was applied to detect the learning and memory ability of mice. Western blot and immunohistochemistry was applied to analyze O-Glycosylation and phosphorylation of Tau and neurofilaments (NFs) proteins, the phosphorylated JNK and ERK and the deposition of Aβ42protein in brain tissues. The assembly function of Tau binding to microtubule was detected by microtubule binding assay and degenerative nerve cells were labeled with Fluoro-Jade B (FJB)ResultCompared with control group, model group mice had longer escape latency and path length with less time spending in target guadrant and the number of crossing hidden platform was decreased. Tau and NFs proteins were hyperphosphorylated, and the Tau binding to microtubule decreased while the O-Glycosylation of neuronal cytoskeleton proteins was reduced in model mice brain compared with control group. The phosphorylated JNK were higher in model group than the other two groups, while ERK1were lower. More deposition of Aβ42proteins and FJB-positive cells were observed in brain tissues of STZ model mice than control group. Compared with the model group, liraglutide-treated group had less escape latency and path length with more time spending in target guadrant and the number of crossing hidden platform increased, liraglutide significantly improved the learning and memory ability of AD mice. The hyperphosphorylated Tau and NFs proteins decreased and the microtubule-binding of Tau increased, and O-Glycosylation of neuronal cytoskeleton proteins increased in liraglutide-treated group compared with model group. The phosphorylated of JNK in liraglutide-treated group were lower than model group, while ERK1were higher. Less deposition of Aβ42proteins and FJB-positive cells were observed in brain tissues of liraglutide-treated group than STZ model group.ConclusionLiraglutide might protect sporadic AD mice from learning and memory impairment induced by STZ i.c.v. injection through improving JNK and ERK phosphorylation in MAPK signaling pathway, enhancing the O-Glycosylation of neuronal cytoskeleton proteins, decreasing the hyperphosphorylation of Tau and NFs proteins and the deposition of Aβ proteins, led to the reduced neurodegeneration.