PRE-084对PS1/APP小鼠学习记忆及内嗅皮层BDNF和Trkb表达的影响

Effect of PRE-084 on learning and memory and the expression of BDNF and Trkb in the entorhinal cortex of PS1/APP mouse

目的探讨sigma-1受体激动剂PRE-084对PS1/APP小鼠内嗅皮层BDNF、TrkB及学习记忆功能的影响。方法将21只6月龄的PS1/APP小鼠随机平分为3组,分别为生理盐水组、PRE-084组、PRE-084和simga-1受体拮抗剂BD1047组,正常C57/BL6J鼠注射生理盐水作为空白对照组,共4组;利用Morris水迷宫测试学习记忆功能,免疫组化、Westernblot检测BDNF和TrkB在内嗅皮层的表达情况。结果PRE-084明显改善PS1/APP小鼠的学习记忆功能,上调了内嗅皮层内BDNF和TrkB表达水平,而sigma-1受体拮抗剂BD1047能够逆转PRE-084的作用。结论PRE-084通过sigma-1受体改善PS1/APP小鼠学习记忆功能可能与上调内嗅皮层BDNF和TrkB水平相关。

Objective To investigate the effect of a Sigma-1 receptor agonist PRE-084 on learning and memory and the expression of BDNF and Trkb in the entorhinal cortex of PS1/APP mouse. Methods 21 PS1/APP mice were randomly divided into three groups（6-month,n=7）： saline（Tg-eontrol）, PRE-084, PRE-084＋BD1047, 7 wild-type C57/ BL6J mice were administered saline as empty control. We performed water maze experiment to evaluate learning and spatital memory, the expressions of BDNF and TrkB in the entorhinal cortex were detected by Immunohistochemistry and Western blot. Results PRE-084 significantly increased learning and memory ability and the expression levels of BDNF and TrkB in entorhinal cortex of PS1/APP mice, and the effect of PRE-084 was antagonized by co-administration of BD1047. Conclusion The improvement of learning and memory ability of PSI/APP mice by PRE-084 via activating the Sigma-1 receptor might be related to the upregulation of BDNF and TrkB expression in entorhinal cortex.