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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Abstract 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.
AbstractList 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.
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.
Author Alcántara-González, Faviola
Arroyo-García, Luis Enrique
Gamboa, Citlalli
Flores, Gonzalo
Zamudio, Sergio
Juarez, Ismael
Mendoza-Perez, Claudia Rebeca
Zaragoza, Néstor
De La Cruz, Fidel
Garcia-Dolores, Fernando
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  surname: Alcántara-González
  fullname: Alcántara-González, Faviola
  organization: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla. 14 Sur 6301, CP: 72570, Puebla, Puebla, México
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  givenname: Claudia Rebeca
  surname: Mendoza-Perez
  fullname: Mendoza-Perez, Claudia Rebeca
  organization: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla. 14 Sur 6301, CP: 72570, Puebla, Puebla, México
– sequence: 3
  givenname: Néstor
  surname: Zaragoza
  fullname: Zaragoza, Néstor
  organization: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla. 14 Sur 6301, CP: 72570, Puebla, Puebla, México
– sequence: 4
  givenname: Ismael
  surname: Juarez
  fullname: Juarez, Ismael
  organization: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla. 14 Sur 6301, CP: 72570, Puebla, Puebla, México
– sequence: 5
  givenname: Luis Enrique
  surname: Arroyo-García
  fullname: Arroyo-García, Luis Enrique
  organization: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla. 14 Sur 6301, CP: 72570, Puebla, Puebla, México
– sequence: 6
  givenname: Citlalli
  surname: Gamboa
  fullname: Gamboa, Citlalli
  organization: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla. 14 Sur 6301, CP: 72570, Puebla, Puebla, México
– sequence: 7
  givenname: Fidel
  surname: De La Cruz
  fullname: De La Cruz, Fidel
  organization: Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México D. F., México
– sequence: 8
  givenname: Sergio
  surname: Zamudio
  fullname: Zamudio, Sergio
  organization: Departamento de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México D. F., México
– sequence: 9
  givenname: Fernando
  surname: Garcia-Dolores
  fullname: Garcia-Dolores, Fernando
  organization: Departamento de Anatomía Patológica, Hospital Regional 1° de Octubre, ISSSTE, D.F., México
– sequence: 10
  givenname: Gonzalo
  surname: Flores
  fullname: Flores, Gonzalo
  email: gonzalo.flores@correo.buap.mx, gonzaloflores56@gmail.com
  organization: Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Universidad Autónoma de Puebla. 14 Sur 6301, CP: 72570, Puebla, Puebla, México
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Snippet Cerebrolysin (Cbl) shows neurotrophic and neuroprotective properties while donepezil (Dnp) is a potent acetylcholinesterase (AChE) inhibitor, both drugs are...
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SubjectTerms Aging
Alzheimer's disease
Amino Acids - pharmacology
Animals
cerebrolysin
dendritic morphology
Dendritic Spines - drug effects
Dendritic Spines - ultrastructure
donepezil
Drug Synergism
Golgi-Cox stain
Indans - pharmacology
Male
Mice
Motor Activity - drug effects
Neuronal Plasticity - drug effects
Nootropic Agents - pharmacology
Piperidines - pharmacology
Prefrontal Cortex - cytology
Prefrontal Cortex - drug effects
Prefrontal Cortex - physiology
Pyramidal Cells - cytology
Pyramidal Cells - drug effects
spine density
Title Combined administration of cerebrolysin and donepezil induces plastic changes in prefrontal cortex in aged mice
URI https://api.istex.fr/ark:/67375/WNG-LHNQTF31-0/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fsyn.21588
https://www.ncbi.nlm.nih.gov/pubmed/22826038
https://search.proquest.com/docview/1039346509
Volume 66
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