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Neuroprotective effects of donepezil against cholinergic depletion

INTRODUCTION: Intraparenchymal injections of the immunotoxin 192-IgG-saporin into medial septum and nucleus basalis magnocellularis causes a selective depletion of basal forebrain cholinergic neurons. Thus, it represents a valid model to mimic a key component of the cognitive deficits associated wit...

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Autores principales: Cutuli, Debora, De Bartolo, Paola, Caporali, Paola, Tartaglione, Anna Maria, Oddi, Diego, D’Amato, Francesca Romana, Nobili, Annalisa, D’Amelio, Marcello, Petrosini, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978431/
https://www.ncbi.nlm.nih.gov/pubmed/24401551
http://dx.doi.org/10.1186/alzrt215
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author Cutuli, Debora
De Bartolo, Paola
Caporali, Paola
Tartaglione, Anna Maria
Oddi, Diego
D’Amato, Francesca Romana
Nobili, Annalisa
D’Amelio, Marcello
Petrosini, Laura
author_facet Cutuli, Debora
De Bartolo, Paola
Caporali, Paola
Tartaglione, Anna Maria
Oddi, Diego
D’Amato, Francesca Romana
Nobili, Annalisa
D’Amelio, Marcello
Petrosini, Laura
author_sort Cutuli, Debora
collection PubMed
description INTRODUCTION: Intraparenchymal injections of the immunotoxin 192-IgG-saporin into medial septum and nucleus basalis magnocellularis causes a selective depletion of basal forebrain cholinergic neurons. Thus, it represents a valid model to mimic a key component of the cognitive deficits associated with aging and dementia. Here we administered donepezil, a potent acetylcholinesterase inhibitor developed for treating Alzheimer’s disease, 15 days before 192-IgG-saporin injection, and thus we examined donepezil effects on neurodegeneration and cognitive deficits. METHODS: Caspase-3 activity and cognitive performances of lesioned rats pre-treated with donepezil or saline were analyzed and compared to the outcomes obtained in pre-treated sham-lesioned rats. RESULTS: Cholinergic depletion increased hippocampal and neocortical caspase-3 activity and impaired working memory, spatial discrimination, social novelty preference, and ultrasonic vocalizations, without affecting anxiety levels and fear conditioning. In lesioned animals, donepezil pre-treatment reduced hippocampal and neocortical caspase-3 activity and improved working memory and spatial discrimination performances and partially rescued ultrasonic vocalizations, without preventing social novelty alterations. CONCLUSIONS: Present data indicate that donepezil pre-treatment exerts beneficial effects on behavioral deficits induced by cholinergic depletion, attenuating the concomitant hippocampal and neocortical neurodegeneration.
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spelling pubmed-39784312014-04-09 Neuroprotective effects of donepezil against cholinergic depletion Cutuli, Debora De Bartolo, Paola Caporali, Paola Tartaglione, Anna Maria Oddi, Diego D’Amato, Francesca Romana Nobili, Annalisa D’Amelio, Marcello Petrosini, Laura Alzheimers Res Ther Research INTRODUCTION: Intraparenchymal injections of the immunotoxin 192-IgG-saporin into medial septum and nucleus basalis magnocellularis causes a selective depletion of basal forebrain cholinergic neurons. Thus, it represents a valid model to mimic a key component of the cognitive deficits associated with aging and dementia. Here we administered donepezil, a potent acetylcholinesterase inhibitor developed for treating Alzheimer’s disease, 15 days before 192-IgG-saporin injection, and thus we examined donepezil effects on neurodegeneration and cognitive deficits. METHODS: Caspase-3 activity and cognitive performances of lesioned rats pre-treated with donepezil or saline were analyzed and compared to the outcomes obtained in pre-treated sham-lesioned rats. RESULTS: Cholinergic depletion increased hippocampal and neocortical caspase-3 activity and impaired working memory, spatial discrimination, social novelty preference, and ultrasonic vocalizations, without affecting anxiety levels and fear conditioning. In lesioned animals, donepezil pre-treatment reduced hippocampal and neocortical caspase-3 activity and improved working memory and spatial discrimination performances and partially rescued ultrasonic vocalizations, without preventing social novelty alterations. CONCLUSIONS: Present data indicate that donepezil pre-treatment exerts beneficial effects on behavioral deficits induced by cholinergic depletion, attenuating the concomitant hippocampal and neocortical neurodegeneration. BioMed Central 2013-10-24 /pmc/articles/PMC3978431/ /pubmed/24401551 http://dx.doi.org/10.1186/alzrt215 Text en Copyright © 2013 Cutuli et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Cutuli, Debora
De Bartolo, Paola
Caporali, Paola
Tartaglione, Anna Maria
Oddi, Diego
D’Amato, Francesca Romana
Nobili, Annalisa
D’Amelio, Marcello
Petrosini, Laura
Neuroprotective effects of donepezil against cholinergic depletion
title Neuroprotective effects of donepezil against cholinergic depletion
title_full Neuroprotective effects of donepezil against cholinergic depletion
title_fullStr Neuroprotective effects of donepezil against cholinergic depletion
title_full_unstemmed Neuroprotective effects of donepezil against cholinergic depletion
title_short Neuroprotective effects of donepezil against cholinergic depletion
title_sort neuroprotective effects of donepezil against cholinergic depletion
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978431/
https://www.ncbi.nlm.nih.gov/pubmed/24401551
http://dx.doi.org/10.1186/alzrt215
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