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


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
Issue number5
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cognitive Neuroscience


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