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Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP

Transient global amnesia, both persistent and transient, is a very common neuropsychiatric syndrome. Among animal models for amnesia and testing new drugs, the scopolamine test is the most widely used for transient global amnesia (TGA). This study examined the scopolamine-induced deficits in working...

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Autores principales: Belardo, Carmela, Boccella, Serena, Perrone, Michela, Fusco, Antimo, Morace, Andrea Maria, Ricciardi, Federica, Bonsale, Roozbe, ELBini-Dhouib, Ines, Guida, Francesca, Luongo, Livio, Bagetta, Giacinto, Scuteri, Damiana, Maione, Sabatino
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532394/
https://www.ncbi.nlm.nih.gov/pubmed/37762702
http://dx.doi.org/10.3390/ijms241814399
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author Belardo, Carmela
Boccella, Serena
Perrone, Michela
Fusco, Antimo
Morace, Andrea Maria
Ricciardi, Federica
Bonsale, Roozbe
ELBini-Dhouib, Ines
Guida, Francesca
Luongo, Livio
Bagetta, Giacinto
Scuteri, Damiana
Maione, Sabatino
author_facet Belardo, Carmela
Boccella, Serena
Perrone, Michela
Fusco, Antimo
Morace, Andrea Maria
Ricciardi, Federica
Bonsale, Roozbe
ELBini-Dhouib, Ines
Guida, Francesca
Luongo, Livio
Bagetta, Giacinto
Scuteri, Damiana
Maione, Sabatino
author_sort Belardo, Carmela
collection PubMed
description Transient global amnesia, both persistent and transient, is a very common neuropsychiatric syndrome. Among animal models for amnesia and testing new drugs, the scopolamine test is the most widely used for transient global amnesia (TGA). This study examined the scopolamine-induced deficits in working memory, discriminative memory, anxiety, and motor activity in the presence of intranasal PEA-OXA, a dual antagonist of presynaptic α2 and H3 receptors. Male C57BL/6 mice were treated with intraperitoneal scopolamine (1 mg/kg) with or without pre-treatment (15 min) or post-treatment (15 min) with intranasal PEA-OXA (10 mg/kg). It was seen that scopolamine induced deficits of discriminative and spatial memory and motor deficit. These changes were associated with a loss of synaptic plasticity in the hippocampal dentate gyrus: impaired LTP after lateral entorhinal cortex/perforant pathway tetanization. Furthermore, hippocampal Ach levels were increased while ChA-T expression was reduced following scopolamine administration. PEA-OXA either prevented or restored the scopolamine-induced cognitive deficits (discriminative and spatial memory). However, the same treatment did not affect the altered motor activity or anxiety-like behavior induced by scopolamine. Consistently, electrophysiological analysis showed LTP recovery in the DG of the hippocampus, while the Ach level and ChoA-T were normalized. This study confirms the neuroprotective and pro-cognitive activity of PEA-OXA (probably through an increase in the extracellular levels of biogenic amines) in improving transient memory disorders for which the available pharmacological tools are obsolete or inadequate and not directed on specific pathophysiological targets.
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spelling pubmed-105323942023-09-28 Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP Belardo, Carmela Boccella, Serena Perrone, Michela Fusco, Antimo Morace, Andrea Maria Ricciardi, Federica Bonsale, Roozbe ELBini-Dhouib, Ines Guida, Francesca Luongo, Livio Bagetta, Giacinto Scuteri, Damiana Maione, Sabatino Int J Mol Sci Article Transient global amnesia, both persistent and transient, is a very common neuropsychiatric syndrome. Among animal models for amnesia and testing new drugs, the scopolamine test is the most widely used for transient global amnesia (TGA). This study examined the scopolamine-induced deficits in working memory, discriminative memory, anxiety, and motor activity in the presence of intranasal PEA-OXA, a dual antagonist of presynaptic α2 and H3 receptors. Male C57BL/6 mice were treated with intraperitoneal scopolamine (1 mg/kg) with or without pre-treatment (15 min) or post-treatment (15 min) with intranasal PEA-OXA (10 mg/kg). It was seen that scopolamine induced deficits of discriminative and spatial memory and motor deficit. These changes were associated with a loss of synaptic plasticity in the hippocampal dentate gyrus: impaired LTP after lateral entorhinal cortex/perforant pathway tetanization. Furthermore, hippocampal Ach levels were increased while ChA-T expression was reduced following scopolamine administration. PEA-OXA either prevented or restored the scopolamine-induced cognitive deficits (discriminative and spatial memory). However, the same treatment did not affect the altered motor activity or anxiety-like behavior induced by scopolamine. Consistently, electrophysiological analysis showed LTP recovery in the DG of the hippocampus, while the Ach level and ChoA-T were normalized. This study confirms the neuroprotective and pro-cognitive activity of PEA-OXA (probably through an increase in the extracellular levels of biogenic amines) in improving transient memory disorders for which the available pharmacological tools are obsolete or inadequate and not directed on specific pathophysiological targets. MDPI 2023-09-21 /pmc/articles/PMC10532394/ /pubmed/37762702 http://dx.doi.org/10.3390/ijms241814399 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Belardo, Carmela
Boccella, Serena
Perrone, Michela
Fusco, Antimo
Morace, Andrea Maria
Ricciardi, Federica
Bonsale, Roozbe
ELBini-Dhouib, Ines
Guida, Francesca
Luongo, Livio
Bagetta, Giacinto
Scuteri, Damiana
Maione, Sabatino
Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP
title Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP
title_full Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP
title_fullStr Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP
title_full_unstemmed Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP
title_short Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP
title_sort scopolamine-induced memory impairment in mice: effects of pea-oxa on memory retrieval and hippocampal ltp
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532394/
https://www.ncbi.nlm.nih.gov/pubmed/37762702
http://dx.doi.org/10.3390/ijms241814399
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