Chronic administration of Tat-GluR23Y ameliorates cognitive dysfunction targeting CREB signaling in rats with amyloid beta neurotoxicity.
Metab Brain Dis
; 36(4): 701-709, 2021 04.
Article
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| MEDLINE
| ID: mdl-33420884
ABSTRACT
Alzheimer's disease (AD) is behaviorally characterized by memory impairments, and pathologically by amyloid ß1-42 (Aß1-42) plaques and tangles. Aß binds to excitatory synapses and disrupts their transmission due to dysregulation of the glutamate receptors. Here we hypothesized that chronic inhibition of the endocytosis of AMPA receptors together with GluN2B subunit of NMDA receptors might improve cognition deficit induced by Aß(1-42) neurotoxicity. Forty male Wistar rats were used in this study and divided into 5 groups Saline + Saline, Aß+Saline, Aß+Ifen (Ifenprodil, 3 nmol /2 weeks), Aß+GluR23Y (Tat-GluR23Y 3 µmol/kg/2 weeks) and Aß+Ifen+GluR23Y (same doses and durations). Aß(1-42) neurotoxicity was induced by intracerebroventricular (ICV) injection of Aß1-42 (2 µg/µl/side), and then animals received the related treatments for 14 days. Cognitive performance of rats and hippocampal level of cAMP-response element-binding (CREB) were evaluated using Morris Water Maze (MWM), and western blotting respectively. Obtained data from the acquisition trials were analyzed by two way Anova and Student T test. Also one way Analysis of variance (ANOVA) with post hoc Tuckey were used to clarify between groups differences in probe test. The Group receiving Aß, showed significant cognition deficit (long latency to platform and short total time spent in target quadrant (TTS), parallel with lower level of hippocampal CREB, versus vehicle group. While, Aß+ GluR23Y exhibited the shortest latency to platform and the longest TTS during the probe test, parallel with the higher hippocampal level of CREB compared with other groups. The present study provides evidence that chronic administration of Tat-GluR23Y; an inhibitor of GluA2-AMPARs endocytosis, successfully restores spatial memory impaired by amyloid beta neurotoxicity targeting CREB signaling pathway.
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Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
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Péptidos beta-Amiloides
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Sistemas de Liberación de Medicamentos
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico
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Péptidos de Penetración Celular
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Disfunción Cognitiva
Idioma:
En
Revista:
Metab Brain Dis
Asunto de la revista:
CEREBRO
/
METABOLISMO
Año:
2021
Tipo del documento:
Article