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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 5/2013

Open Access 01-10-2013 | Research

Neuroprotective effects of donepezil against cholinergic depletion

Authors: Debora Cutuli, Paola De Bartolo, Paola Caporali, Anna Maria Tartaglione, Diego Oddi, Francesca Romana D’Amato, Annalisa Nobili, Marcello D’Amelio, Laura Petrosini

Published in: Alzheimer's Research & Therapy | Issue 5/2013

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Abstract

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.
Appendix
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Metadata
Title
Neuroprotective effects of donepezil against cholinergic depletion
Authors
Debora Cutuli
Paola De Bartolo
Paola Caporali
Anna Maria Tartaglione
Diego Oddi
Francesca Romana D’Amato
Annalisa Nobili
Marcello D’Amelio
Laura Petrosini
Publication date
01-10-2013
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 5/2013
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/alzrt215

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