Co-treatment of AMPA endocytosis inhibitor and GluN2B antagonist facilitate consolidation and retrieval of memory impaired by ß amyloid peptide.
Int J Neurosci
; 132(7): 714-723, 2022 Jul.
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| ID: mdl-33115292
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 (Aß).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 Aß1-42 (2 µg/µl), and evaluated using Morris Water Maze (MWM). Each experiment consisted of 5 groups Saline + Saline, Aß + Saline, Aß + Ifenprodil (Ifen, 3 nmol/ICV), Aß +Tat-GluR23Y (3 µmol/kg/IP), and Aß1 +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, Aß+ 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 Aß + 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 Aß + Tat-GluR23Y (p = 0.001) and Aß+ 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 Aß induced memory impairment via the CREB signaling pathway.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
/
Receptores de N-Metil-D-Aspartato
Idioma:
En
Revista:
Int J Neurosci
Año:
2022
Tipo del documento:
Article