Co-treatment of AMPA endocytosis inhibitor and GluN2B antagonist facilitate consolidation and retrieval of memory impaired by β amyloid peptide

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.

Graphical abstract

Keywords:

• Glutamate
• spatial memory
• CREB
• consolidation
• retrieval
• MWM

Acknowledgments

The authors would like to thank Dr Bahram Soltani, Head of the Cellular & Molecular Research Center and Department of pharmacology for their laboratory facilities and technical support.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was a master science student thesis has been financially supported by the grant (No IR.GUMS.REC.1396.264) from Research deputy of Guilan University of Medical Sciences, Rasht, Iran.