蛋白酶体抑制剂MG132对小鼠一次性被动回避实验记忆形成和提取的作用

Effects of proteasome inhibitor MG132 on memory acquisition and retrieval in one-trial passive avoidance in mice

目的 探索蛋白酶体抑制剂MG132对小鼠被动回避实验学习记忆的作用.方法 在不同时间点皮下注射MG132 （25mg/kg）测定海马区蛋白酶体系统活性的变化.在一次性被动回避实验训练前或测试前皮下注射蛋白酶体抑制剂MG132 （25 mg/kg）,之后测定MG132对记忆形成和记忆提取的影响.采用皮下注射MG132 （12mg/kg）和新奇环境干扰,测定MG132对干扰引起的记忆提取障碍的作用.结果 皮下注MG132（25 mg/kg）0.5～1.5 h后海马蛋白酶体系统被显著抑制.训练前以及测试前皮下注射MG132的记忆时间[分别为：训练前（173.30±47.51）s,测试前（44.10±11.16）s],低于对照组记忆测试结果[分别为：训练前对照组（296.03±3.97）s,测试前对照组（199.23 ±43.01）s],差异有统计学意义（P＜0.05）.测试前给予新环境干扰[（184.30±50）s]有降低记忆时间的趋势[对照组（287.37±12.63）s],而加入MG132后记忆测试[（84.70±23.92）s]显著低于对照组[（164.02±35.26）s],差异有统计学意义（P＜0.05）.但MG132自身对测试结果无统计学意义[实验组（150.10±35.89）s,对照组（174.19±30.54）s].结论 皮下注射MG132抑制海马区蛋白酶体活性进而阻碍小鼠一次性被动回避记忆形成及提取,并且放大干扰造成的记忆提取障碍.

Objective To investigate the effects of proteasome inhibitor MG132 on memory acquisition and memory retrieval in one-trail passive avoidance for mice.Methods MG132 （25 mg/kg） was administrated at different time points to analyze the time-dependent effects of MG132 on hippocampus proteasome activity.MG132 （25 mg/kg） was administrated 3 hours before-training or 1.5 hours pre-test to investigate the effect on memory acquisition and retrieval.The interaction of low dose （12 mg/kg） of MG132 and novelty interference on memory retrieval to studied.Results Hippocampus proteasome activity was significantly blocked when MG132 （25 mg/kg） was administrated 0.5-1.5 hours before analysis.The inhibition recovered as time passing and backed to normal state 24 hours later.A significant difference was showed between vehicle and pre-training,pre-test group （pre-training vehicle （296.03 ± 3.97） s,pre-training （173.30 ± 47.51） s ; pre-test vehicle （199.23 ± 43.01） s,pre-test （44.10 ± 11.16） s）.Proteasome inhibitor did not produce a significant effect on memory retrieval （vehicle （174.19 ± 30.54）s,lower dose （174.19± 30.54）s）,then only together with a novelty task the retrieval was significantly altered（vehicle （164.02 ±35.26）s,MG132 ＋novelty group （84.70 ±23.92）s）.Conclusion Proteasome inhibitor MG132 can inhibit memory acquisition and memory retrieval.Thereby the effect on memory retrieval is enhanced by novelty.Thus,a physiological proteasome activity is essential for learning abilities.