title: Neuroprotective effects of donepezil against cholinergic depletion.
abstract: BACKGROUND
  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.
authors.forename: Debora
authors.initials: D
authors.lastname: Cutuli
authors.forename: Paola
authors.initials: P
authors.lastname: De Bartolo
authors.forename: Paola
authors.initials: P
authors.lastname: Caporali
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Tartaglione
authors.forename: Diego
authors.initials: D
authors.lastname: Oddi
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: D'Amato
authors.forename: Annalisa
authors.initials: A
authors.lastname: Nobili
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Amelio
authors.forename: Laura
authors.initials: L
authors.lastname: Petrosini