Neuroprotective effects of donepezil against cholinergic depletion

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number50
JournalAlzheimer's Research and Therapy
Volume5
Issue number5
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cognitive Neuroscience

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