Abstract

Background

Glutamate neurotransmission stands as an important issue to minimize memory impairment. We investigated the effects of an inhibitor of α-amino-3-hydroxy-5-methyl-4-isozazole propionic acid receptors (AMPA) endocytosis and GluN2B subunit of N-methyl-d-aspartate receptors (NMDA), either isolated or combined, on memory impairments induced by Amyloid beta1-42 (Aβ).

Methods

Eighty male Wistar rats were used for two experiments of consolidation and retrieval of memory. Memory impairment was induced by intracerebroventricular (ICV) injection of Aβ1-42 (2 μg/μl), and evaluated using Morris Water Maze (MWM). Each experiment consisted of 5 groups: Saline + Saline, Aβ + Saline, Aβ + Ifenprodil (Ifen, 3 nmol/ICV), Aβ +Tat-GluR23Y (3 µmol/kg/IP), and Aβ1 +Ifen + Tat-GluR23Y. Then, hippocampal cAMP-response element-binding protein (CREB) was measured by western blotting. Data were analyzed by Analysis of variance (ANOVA) repeated measure, and one-way Anova followed by Tukey’s post hoc test.

Results

During retrieval, Aβ+ Tat-GluR23Y showed significant improvement in total time spent (TTS) in the target quadrant (p = 0.009), escape latency to a platform (p = 0.008) and hippocampal level of CREB (p = 0.006) compared with Aβ + saline. Also, coadministration of Tat-GluR23Yand Ifen similar to Tat-GluR23Y alone caused significant improvement in TTS (p = 0.014) and latency to platform (p = 0.013). During consolidation, shorter escape latency (p = 0.001), longer TTS (p = 0.002) and higher level of hippocampal CREB were observed in the Aβ + Tat-GluR23Y (p = 0.001) and Aβ+ Tat-GluR23Y + Ifen (p = 0.017), respectively.

Conclusion

The present study provides pieces of evidence that inhibition of AMPARs endocytosis using Tat-GluR23Y facilitates memory consolidation and retrieval in Aβ induced memory impairment via the CREB signaling pathway.

中文翻译：

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AMPA 内吞抑制剂和 GluN2B 拮抗剂的共同治疗促进β淀粉样肽受损记忆的巩固和恢复

摘要

背景

谷氨酸神经传递是减少记忆障碍的一个重要问题。我们研究了α-氨基-3-羟基-5-甲基-4-异唑丙酸受体 (AMPA) 内吞作用和 N-甲基-d-天冬氨酸受体 (NMDA) 的 GluN2B 亚基的抑制剂的作用，无论是分离的还是组合的，关于由淀粉样蛋白 beta1-42 (Aβ) 引起的记忆障碍。

方法

80 只雄性 Wistar 大鼠用于记忆巩固和恢复的两个实验。通过脑室内 (ICV) 注射 Aβ1-42 (2 μg/μl) 诱导记忆障碍，并使用 Morris Water Maze (MWM) 进行评估。每个实验由 5 组组成：盐水 + 盐水、Aβ + 盐水、Aβ + Ifenprodil (Ifen, 3 nmol/ICV)、Aβ +Tat-GluR23Y (3 µmol/kg/IP) 和 Aβ1 + Ifen + Tat-GluR23Y。然后，通过蛋白质印迹测量海马 cAMP 反应元件结合蛋白 (CREB)。通过方差分析 (ANOVA) 重复测量和单向 Anova 分析数据，然后进行 Tukey 事后检验。

结果

在检索过程中，Aβ+ Tat-GluR23Y 在目标象限 ( p  = 0.009)、逃逸潜伏期 ( p  = 0.008) 和海马 CREB ​​水平 ( p  = 0.006)方面显示出显着改善。 Aβ + 生理盐水。此外，与单独使用 Tat-GluR23Y 类似的 Tat-GluR23Y 和 Ifen 的共同给药导致 TTS ( p  = 0.014) 和平台延迟 ( p  = 0.013) 的显着改善。在巩固过程中，在 Aβ + Tat-  GluR23Y  ( p = 0.001) 和 Aβ + Tat- GluR23Y  + Ifen ( p = 0.017），分别。

结论

本研究提供的证据表明，使用 Tat-GluR23Y 抑制 AMPAR 内吞作用通过CREB ​​信号通路促进A β 诱导的记忆障碍中的记忆巩固和恢复。