Combined administration of cerebrolysin and donepezil induces plastic changes in prefrontal cortex in aged mice

Cerebrolysin (Cbl) shows neurotrophic and neuroprotective properties while donepezil (Dnp) is a potent acetylcholinesterase (AChE) inhibitor, both drugs are prescribed for Alzheimer's disease (AD) treatment. Previous studies have shown that the Dnp and Cbl administered separately, modify dendri...

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Published inSynapse (New York, N.Y.) Vol. 66; no. 11; pp. 938 - 949
Main Authors Alcántara-González, Faviola, Mendoza-Perez, Claudia Rebeca, Zaragoza, Néstor, Juarez, Ismael, Arroyo-García, Luis Enrique, Gamboa, Citlalli, De La Cruz, Fidel, Zamudio, Sergio, Garcia-Dolores, Fernando, Flores, Gonzalo
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2012
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Summary:Cerebrolysin (Cbl) shows neurotrophic and neuroprotective properties while donepezil (Dnp) is a potent acetylcholinesterase (AChE) inhibitor, both drugs are prescribed for Alzheimer's disease (AD) treatment. Previous studies have shown that the Dnp and Cbl administered separately, modify dendritic morphology of neurons in the prefrontal cortex and hippocampus in senile rodents. Since the deficit of neurotrophic factor activity is implicated in the degeneration of cholinergic neurons of basal forebrain, a combination therapy of Dnp and Cbl has been tested recently in Alzheimer's patients. However, the plastic changes that may underlie this combined treatment have not yet been explored. We present here the effect of the combined administration of Cbl and Dnp on dendritic morphology in brain regions related to learning and memory in aged mice. The Golgi‐Cox staining protocol and Sholl analysis were used for studying dendritic changes. Cbl and Dnp were administrated daily for 2 months to 9‐months‐old mice. Locomotor activity was assessed, as well as the dendritic morphology of neurons in several limbic regions was analyzed. Results showed that Cbl and Dnp induced an increase in locomotor activity without synergistic effect. The Cbl or Dnp treatment modified the dendritic morphology of neurons from prefrontal cortex (PFC), dorsal hippocampus (DH), dentate gyrus (DG), and the shell of nucleus accumbens (NAcc). These changes show an increase in the total dendritic length and spine density, resulting in an improvement of dendritic arborization. Prominently, a synergistic effect of Cbl and Dnp was observed on branching order and total dendritic length of pyramidal neurons from PFC. These results suggest that Dnp and Cbl may induce plastic changes in a manner independent of each other, but could enhance their effect in target cells from PFC. Synapse 66:938–949, 2012. © 2012 Wiley Periodicals, Inc.
Bibliography:VIEP-BUAP - No. FLAG-SAL12-Ind
CONACYT - No. 129303; No. 138663
istex:57137F1C0BBF0CE0DD2D6606DABBB6E8EAACB8DE
ArticleID:SYN21588
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ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0887-4476
1098-2396
DOI:10.1002/syn.21588