IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function

Autores
Pardo, Joaquin; Abba, Martín Carlos; Lacunza, Ezequiel; Ogundele, Olalekan Michael; Paiva, Isabel; Morel, Gustavo Ramón; Outeiro, Tiago F.; Goya, Rodolfo Gustavo
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28 months old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.
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: Abba, Martín Carlos. Universidad Nacional de La Plata; Argentina
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata; Argentina
Fil: Ogundele, Olalekan Michael. State University of Louisiana; Estados Unidos
Fil: Paiva, Isabel. 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: Outeiro, Tiago F.. Universität Göttingen; Alemania. Max Planck Institute for Experimental Medicine; Alemania
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
Igf1
Brain
Gene Expression
Ngs
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:11336/49870
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/49870
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory FunctionPardo, JoaquinAbba, Martín CarlosLacunza, EzequielOgundele, Olalekan MichaelPaiva, IsabelMorel, Gustavo RamónOuteiro, Tiago F.Goya, Rodolfo GustavoIgf1BrainGene ExpressionNgshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28 months old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.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: Abba, Martín Carlos. Universidad Nacional de La Plata; ArgentinaFil: Lacunza, Ezequiel. Universidad Nacional de La Plata; ArgentinaFil: Ogundele, Olalekan Michael. State University of Louisiana; Estados UnidosFil: Paiva, Isabel. 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: Outeiro, Tiago F.. Universität Göttingen; Alemania. Max Planck Institute for Experimental Medicine; AlemaniaFil: 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 ; ArgentinaGerontological Soc Amer2017-06info: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/11336/49870Pardo, Joaquin; Abba, Martín Carlos; Lacunza, Ezequiel; Ogundele, Olalekan Michael; Paiva, Isabel; et al.; IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function; Gerontological Soc Amer; Journals Of Gerontology Series A-biological Sciences And Medical Sciences; 72; 4; 6-2017; 459-4671079-5006CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/gerona/glx125info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biomedgerontology/article-abstract/73/4/459/3884478?redirectedFrom=fulltextinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:01:37Zoai:ri.conicet.gov.ar:11336/49870instacron: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:34982025-09-10 13:01:38.058CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
title IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
spellingShingle IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
Pardo, Joaquin
Igf1
Brain
Gene Expression
Ngs
title_short IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
title_full IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
title_fullStr IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
title_full_unstemmed IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
title_sort IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function
dc.creator.none.fl_str_mv Pardo, Joaquin
Abba, Martín Carlos
Lacunza, Ezequiel
Ogundele, Olalekan Michael
Paiva, Isabel
Morel, Gustavo Ramón
Outeiro, Tiago F.
Goya, Rodolfo Gustavo
author Pardo, Joaquin
author_facet Pardo, Joaquin
Abba, Martín Carlos
Lacunza, Ezequiel
Ogundele, Olalekan Michael
Paiva, Isabel
Morel, Gustavo Ramón
Outeiro, Tiago F.
Goya, Rodolfo Gustavo
author_role author
author2 Abba, Martín Carlos
Lacunza, Ezequiel
Ogundele, Olalekan Michael
Paiva, Isabel
Morel, Gustavo Ramón
Outeiro, Tiago F.
Goya, Rodolfo Gustavo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Igf1
Brain
Gene Expression
Ngs
topic Igf1
Brain
Gene Expression
Ngs
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28 months old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.
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: Abba, Martín Carlos. Universidad Nacional de La Plata; Argentina
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata; Argentina
Fil: Ogundele, Olalekan Michael. State University of Louisiana; Estados Unidos
Fil: Paiva, Isabel. 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: Outeiro, Tiago F.. Universität Göttingen; Alemania. Max Planck Institute for Experimental Medicine; Alemania
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 normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28 months old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.
publishDate 2017
dc.date.none.fl_str_mv 2017-06
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/11336/49870
Pardo, Joaquin; Abba, Martín Carlos; Lacunza, Ezequiel; Ogundele, Olalekan Michael; Paiva, Isabel; et al.; IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function; Gerontological Soc Amer; Journals Of Gerontology Series A-biological Sciences And Medical Sciences; 72; 4; 6-2017; 459-467
1079-5006
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49870
identifier_str_mv Pardo, Joaquin; Abba, Martín Carlos; Lacunza, Ezequiel; Ogundele, Olalekan Michael; Paiva, Isabel; et al.; IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function; Gerontological Soc Amer; Journals Of Gerontology Series A-biological Sciences And Medical Sciences; 72; 4; 6-2017; 459-467
1079-5006
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/gerona/glx125
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biomedgerontology/article-abstract/73/4/459/3884478?redirectedFrom=fulltext
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 Gerontological Soc Amer
publisher.none.fl_str_mv Gerontological Soc Amer
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 12.993085

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