Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats

Autores
Pardo, Joaquin; Uriarte Donati, Maia; Cónsole, Gloria M.; Reggiani, Paula Cecilia; Outeiro, Tiago F.; Morel, Gustavo Ramón; Goya, Rodolfo Gustavo
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age‐related cognitive deficits. Some of these strategies involve neurotrophic factors like insulin‐like growth factor‐I (IGF‐I), a powerful neuroprotective molecule in the brain. Here, we implemented 18‐day long intracerebroventricular (ICV) IGF‐I gene therapy in 28 months old Sprague–Dawley female rats, and assessed spatial memory performance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectors expressing the gene for rat IGF‐I or the reporter DsRed were used. Cerebrospinal fluid (CSF) samples were taken and IGF‐I levels determined by radioimmunoassay. At the end of the study, IGF‐I levels in the CSF were significantly higher in the experimental group than in the DsRed controls. After treatment, the IGF‐I group showed a significant improvement in spatial memory accuracy as compared with DsRed counterparts. In the dentate gyrus (DG) of the hippocampus, the IGF‐I group showed a higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching and reduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach to increase CSF levels of IGF‐I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect of the treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performance in aging rats.
Fil: Pardo, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Uriarte Donati, Maia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Cónsole, Gloria M.. Universidad Nacional de La Plata; Argentina
Fil: Reggiani, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Outeiro, Tiago F.. Universität Göttingen; Alemania
Fil: Morel, Gustavo Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Materia
Aging
Barnes Maze
Gene Therapy
Hippocampal Morphology
Igf-I
Spatial Memory
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/48899
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging ratsPardo, JoaquinUriarte Donati, MaiaCónsole, Gloria M.Reggiani, Paula CeciliaOuteiro, Tiago F.Morel, Gustavo RamónGoya, Rodolfo GustavoAgingBarnes MazeGene TherapyHippocampal MorphologyIgf-ISpatial Memoryhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age‐related cognitive deficits. Some of these strategies involve neurotrophic factors like insulin‐like growth factor‐I (IGF‐I), a powerful neuroprotective molecule in the brain. Here, we implemented 18‐day long intracerebroventricular (ICV) IGF‐I gene therapy in 28 months old Sprague–Dawley female rats, and assessed spatial memory performance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectors expressing the gene for rat IGF‐I or the reporter DsRed were used. Cerebrospinal fluid (CSF) samples were taken and IGF‐I levels determined by radioimmunoassay. At the end of the study, IGF‐I levels in the CSF were significantly higher in the experimental group than in the DsRed controls. After treatment, the IGF‐I group showed a significant improvement in spatial memory accuracy as compared with DsRed counterparts. In the dentate gyrus (DG) of the hippocampus, the IGF‐I group showed a higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching and reduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach to increase CSF levels of IGF‐I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect of the treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performance in aging rats.Fil: Pardo, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Uriarte Donati, Maia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Cónsole, Gloria M.. Universidad Nacional de La Plata; ArgentinaFil: Reggiani, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Outeiro, Tiago F.. Universität Göttingen; AlemaniaFil: Morel, Gustavo Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaWiley Blackwell Publishing, Inc2016-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48899Pardo, Joaquin; Uriarte Donati, Maia; Cónsole, Gloria M.; Reggiani, Paula Cecilia; Outeiro, Tiago F.; et al.; Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats; Wiley Blackwell Publishing, Inc; European Journal Of Neuroscience; 44; 4; 5-2016; 2120-21280953-816XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/ejn.13278info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:40Zoai:ri.conicet.gov.ar:11336/48899instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:49:40.954CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
title Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
spellingShingle Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
Pardo, Joaquin
Aging
Barnes Maze
Gene Therapy
Hippocampal Morphology
Igf-I
Spatial Memory
title_short Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
title_full Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
title_fullStr Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
title_full_unstemmed Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
title_sort Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats
dc.creator.none.fl_str_mv Pardo, Joaquin
Uriarte Donati, Maia
Cónsole, Gloria M.
Reggiani, Paula Cecilia
Outeiro, Tiago F.
Morel, Gustavo Ramón
Goya, Rodolfo Gustavo
author Pardo, Joaquin
author_facet Pardo, Joaquin
Uriarte Donati, Maia
Cónsole, Gloria M.
Reggiani, Paula Cecilia
Outeiro, Tiago F.
Morel, Gustavo Ramón
Goya, Rodolfo Gustavo
author_role author
author2 Uriarte Donati, Maia
Cónsole, Gloria M.
Reggiani, Paula Cecilia
Outeiro, Tiago F.
Morel, Gustavo Ramón
Goya, Rodolfo Gustavo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Aging
Barnes Maze
Gene Therapy
Hippocampal Morphology
Igf-I
Spatial Memory
topic Aging
Barnes Maze
Gene Therapy
Hippocampal Morphology
Igf-I
Spatial Memory
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age‐related cognitive deficits. Some of these strategies involve neurotrophic factors like insulin‐like growth factor‐I (IGF‐I), a powerful neuroprotective molecule in the brain. Here, we implemented 18‐day long intracerebroventricular (ICV) IGF‐I gene therapy in 28 months old Sprague–Dawley female rats, and assessed spatial memory performance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectors expressing the gene for rat IGF‐I or the reporter DsRed were used. Cerebrospinal fluid (CSF) samples were taken and IGF‐I levels determined by radioimmunoassay. At the end of the study, IGF‐I levels in the CSF were significantly higher in the experimental group than in the DsRed controls. After treatment, the IGF‐I group showed a significant improvement in spatial memory accuracy as compared with DsRed counterparts. In the dentate gyrus (DG) of the hippocampus, the IGF‐I group showed a higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching and reduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach to increase CSF levels of IGF‐I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect of the treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performance in aging rats.
Fil: Pardo, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Uriarte Donati, Maia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Cónsole, Gloria M.. Universidad Nacional de La Plata; Argentina
Fil: Reggiani, Paula Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Outeiro, Tiago F.. Universität Göttingen; Alemania
Fil: Morel, Gustavo Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
Fil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina
description In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age‐related cognitive deficits. Some of these strategies involve neurotrophic factors like insulin‐like growth factor‐I (IGF‐I), a powerful neuroprotective molecule in the brain. Here, we implemented 18‐day long intracerebroventricular (ICV) IGF‐I gene therapy in 28 months old Sprague–Dawley female rats, and assessed spatial memory performance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectors expressing the gene for rat IGF‐I or the reporter DsRed were used. Cerebrospinal fluid (CSF) samples were taken and IGF‐I levels determined by radioimmunoassay. At the end of the study, IGF‐I levels in the CSF were significantly higher in the experimental group than in the DsRed controls. After treatment, the IGF‐I group showed a significant improvement in spatial memory accuracy as compared with DsRed counterparts. In the dentate gyrus (DG) of the hippocampus, the IGF‐I group showed a higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching and reduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach to increase CSF levels of IGF‐I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect of the treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performance in aging rats.
publishDate 2016
dc.date.none.fl_str_mv 2016-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/48899
Pardo, Joaquin; Uriarte Donati, Maia; Cónsole, Gloria M.; Reggiani, Paula Cecilia; Outeiro, Tiago F.; et al.; Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats; Wiley Blackwell Publishing, Inc; European Journal Of Neuroscience; 44; 4; 5-2016; 2120-2128
0953-816X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48899
identifier_str_mv Pardo, Joaquin; Uriarte Donati, Maia; Cónsole, Gloria M.; Reggiani, Paula Cecilia; Outeiro, Tiago F.; et al.; Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats; Wiley Blackwell Publishing, Inc; European Journal Of Neuroscience; 44; 4; 5-2016; 2120-2128
0953-816X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/ejn.13278
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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