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

Faviola Alcántara‐González; Claudia Rebeca Mendoza‐Perez; Néstor Zaragoza; Ismael Juárez; Luis Enrique Arroyo‐García; Citlalli Gamboa; Fidel De La Cruz; Sergio Zamudio; Fernando Garcia‐Dolores; Gonzalo Flores

doi:10.1002/syn.21588

journal article Aug 13, 2012

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

Faviola Alcántara‐González Claudia Rebeca Mendoza‐Perez Néstor Zaragoza Ismael Juárez Luis Enrique Arroyo‐García Citlalli Gamboa Fidel De La Cruz Sergio Zamudio Fernando Garcia‐Dolores Gonzalo Flores

Synapse Vol. 66 No. 11 pp. 938-949 · Wiley

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Abstract

AbstractCerebrolysin (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.

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Details

Published: Aug 13, 2012
Vol/Issue: 66(11)
Pages: 938-949
License: View

Authors

F

Faviola Alcántara‐González

C

Claudia Rebeca Mendoza‐Perez

Luis Enrique Arroyo‐García

Fernando Garcia‐Dolores

G

Gonzalo Flores

Cite This Article

Faviola Alcántara‐González, Claudia Rebeca Mendoza‐Perez, Néstor Zaragoza, et al. (2012). Combined administration of cerebrolysin and donepezil induces plastic changes in prefrontal cortex in aged mice. Synapse, 66(11), 938-949. https://doi.org/10.1002/syn.21588

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

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