Effects Of Trehalose On Learning And Memory Impairment Induced By Of Isolfurane In APP Transgenic Mice

Objective：In this thesis, we investigated the effects of inhalationanesthestic isoflurane on the learning-memory ability of APP transgenicmice. Moreover, evaluave the protection from trehalose, and discusstrehalose protection targets.Methods：(1) Divide60healthy12-month mice into three groupsrandomly: control group, Iso group, and Iso+Tre group.(2)30mins beforeanaesthesia, treat the mice in Iso+Tre group with trehalose（400μg/kgin2ml nomal saline）through intraperitoneal injection. For the mice inIso group, firstly,2ml nomal saline was intraperitoneal injected;secondly, induce the two groups of mice with3%inhalation anesthesticisoflurane; thirdly, after the disappearance of righting reflex (whichmight take about10±2min), continue the anaesthesia with1.4%inhalationanesthestic isoflurane for2hours. During the anaesthesia, theconcentration of inhalation oxygen was60%, and the flow speed was1L/min.(3) In the meantime, mice in control group inhaled60%oxygen only.(4)After anaesthesia, divide the mice into two groups randomly.(5) The micein the first group were used for behavior testing, and the mice in thesecond group were utilized for gene testing.Results：In part one, we studied the influence from inhalationanesthestic isoflurane on the behaviors and the protection from trehaloseon the learning-memory ability of APP transgenic mice. The results fromMorris water maze and place navigation test (day one to day four) indicated an obvious extension on the mean escape latency of the mice in Iso group(p<0.01); however, in comparison with the mice in Iso group, ansignificant reduction in the mean escape latency was observed on the micein Iso+Tre group(p<0.05). There was no obvious difference on the meanescape latency from Iso+Tre group and control group.In part two, we investigated the influence of inhalation anesthesticisoflurane on hippocampal neuron apoptosis and the production of Aβ.(1)TUNEL assay demonstrated that the enhancement of the amount of stainingpositive cells in hippocampus CA1region of the mice in Iso group.(2)ELISA assay showed that the amount of Aβ1-42from the mice of Iso groupwas greatly higher than the one from the control group.(3) The resultsfrom Western-blot testing showed that Bax and Caspase-3were enhancedgreatly on the mice from Iso group and Iso+Tre group.Conclusion：(1) Isoflurane could damage the learning-memory abilityof APP transgenic mice.(2) Trehalose prevented the APP transgenic micefrom the damage caused by inhalation anesthestic isoflurane.