黄芩素逆转阿尔茨海默病模型小鼠突触可塑性与认知损害-神经病学专业毕业论文.docxVIP

Abst Abstract Abst Abstract IV IV PAGE PAGE V ABSTRACT Objectives： Increasing evidence suggests that disruptions of synaptic functions correlates with the severity of cognitive deficit in Alzheimer’s disease (AD). Our previous study demonstrates that baicalein enhance NMDAR-dependent LTP in acute rat hippocampal slices. Given that baicalein possess various biological activities, especially its effects on synaptic plasticity and cognitive function, we examined the effect of baicalein on synaptic function in an AD model in vivo. Methods： Baicalein was administered orally via drinking water to the APP/PS1 mice and age-matched wild-type C57BL/6J mice. Treatment started at 5 months of age and mice were assessed for cognition and AD-like pathology at 7-month-old. Learning and memory in mice was analyzed by Morris water maze test, fear conditioning test, and novel object recognition test. Phosphorylation of Akt (at Ser473), glycogen synthase kinase 3β inactive form (GSK3β-Ser-9) and the active GSK3β form (GSK3β-Tyr-216), and β-secretase enzyme (BACE1) were analysed by Western blot. The level of Aβ was quantified by a human Aβ40 or Aβ42 enzyme-linked immunosorbent assay (ELISA ) kits. The LTP at the schaffer collateral-CA1 pathways in mouse hippocampal slices were investigated by electrophysiological methods. The levels of several synaptic proteins in synaptoneurosomes from hippocampus of mice were measured by Western blot. The density of dendritic spines along individual dendrites of pyramidal neurons in hippocampus CA1 region and cortex were evaluated by Golgi-cox staining. Results： The transgenic mice that received baicalein treatment significantly elevated p-Akt at serine 473 in comparison to that of water-treated APP/PS1 mice (P 0.05). No difference in the total protein expressions of Akt was observed between four groups (P 0.05). The reduced level of p-GSK3β-Ser9 in water-treated transgenic mice was fully reversed by administration of baicalein (P 0.05