TY - JOUR
T1 - Neuroprotective effects of donepezil against cholinergic depletion
AU - Cutuli, Debora
AU - De Bartolo, Paola
AU - Caporali, Paola
AU - Tartaglione, Anna Maria
AU - Oddi, Diego
AU - D'Amato, Francesca Romana
AU - Nobili, Annalisa
AU - D'Amelio, Marcello
AU - Petrosini, Laura
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84888330256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888330256&partnerID=8YFLogxK
U2 - 10.1186/alzrt215
DO - 10.1186/alzrt215
M3 - Article
AN - SCOPUS:84888330256
VL - 5
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
SN - 1758-9193
IS - 5
M1 - 50
ER -