Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior

Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of Igf-I in the nervous system (Igf-I¿/¿), and demonstrated that long-term potenti...

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Autores: Herrero-Labrador, Raquel, Fernández Irigoyen, Joaquín, Vecino, Rebeca, González-Arias, Canela, Ausín, Karina, Crespo, Inmaculada, Fernández Acosta, Francisco J., Nieto-Estévez, Vanesa, Román, M. José, Perea, Gertrudis, Torres-Alemán, Ignacio, Santamaría Martínez, Enrique, Vicario, Carlos
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/46547
Acesso em linha:https://hdl.handle.net/2454/46547
Access Level:acceso abierto
Palavra-chave:Insulin-like growth factor-I (IGF-I)
Igf-I deletion
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repository_id_str
spelling Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behaviorHerrero-Labrador, RaquelFernández Irigoyen, JoaquínVecino, RebecaGonzález-Arias, CanelaAusín, KarinaCrespo, InmaculadaFernández Acosta, Francisco J.Nieto-Estévez, VanesaRomán, M. JoséPerea, GertrudisTorres-Alemán, IgnacioSantamaría Martínez, EnriqueVicario, CarlosInsulin-like growth factor-I (IGF-I)Igf-I deletionInsulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of Igf-I in the nervous system (Igf-I¿/¿), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreover, Igf-I¿/¿ mice showed spatial memory deficits in the Morris water maze, and the significant sex-dependent differences displayed by Igf-ICtrl/Ctrl mice disappeared in Igf-I¿/¿ mice in the open field and rota-rod tests. Brain Igf-I deletion disorganized the granule cell layer of the dentate gyrus (DG), and it modified the relative expressions of GAD and VGLUT1, which are preferentially localized to inhibitory and excitatory presynaptic terminals. Furthermore, Igf-I deletion altered protein modules involved in receptor trafficking, synaptic proteins, and proteins that functionally interact with estrogen and androgen metabolism. Our findings indicate that brain IGF-I is crucial for long-term potentiation, and that it is involved in the regulation of spatial memory and sexual dimorphic behaviors, possibly by maintaining the granule cell layer structure and the stability of synaptic-related protein modules.This work was funded by grants from the Spanish “Ministerio Ciencia, Innovación y Universidades, and the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación” (MICIU and MICINN/AEI SAF2016-80419-R, PID2019-109059RB-100, and CIBERNED CB06/05/0065 to C Vicario; PID2019-110356RB-I00/AEI/10.13039/501100011033 to J Fernández-Irigoyen and E Santamaría; PID2019-104376RB-I00 to I Torres-Alemán; and PID2019-106579RB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe to G Perea, and BES-2017-080303 to C González-Arias.Life Science AllianceCiencias de la SaludOsasun Zientziak2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2454/46547reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglésinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109059RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104376RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106579RB-I00info:eu-repo/grantAgreement/ AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BES-2017-080303© 2023 Herrero-Labrador et al. : This article is available under a Creative Commons License (Attribution 4.0 International).https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/465472026-06-17T12:41:47Z
dc.title.none.fl_str_mv Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
title Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
spellingShingle Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
Herrero-Labrador, Raquel
Insulin-like growth factor-I (IGF-I)
Igf-I deletion
title_short Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
title_full Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
title_fullStr Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
title_full_unstemmed Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
title_sort Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior
dc.creator.none.fl_str_mv Herrero-Labrador, Raquel
Fernández Irigoyen, Joaquín
Vecino, Rebeca
González-Arias, Canela
Ausín, Karina
Crespo, Inmaculada
Fernández Acosta, Francisco J.
Nieto-Estévez, Vanesa
Román, M. José
Perea, Gertrudis
Torres-Alemán, Ignacio
Santamaría Martínez, Enrique
Vicario, Carlos
author Herrero-Labrador, Raquel
author_facet Herrero-Labrador, Raquel
Fernández Irigoyen, Joaquín
Vecino, Rebeca
González-Arias, Canela
Ausín, Karina
Crespo, Inmaculada
Fernández Acosta, Francisco J.
Nieto-Estévez, Vanesa
Román, M. José
Perea, Gertrudis
Torres-Alemán, Ignacio
Santamaría Martínez, Enrique
Vicario, Carlos
author_role author
author2 Fernández Irigoyen, Joaquín
Vecino, Rebeca
González-Arias, Canela
Ausín, Karina
Crespo, Inmaculada
Fernández Acosta, Francisco J.
Nieto-Estévez, Vanesa
Román, M. José
Perea, Gertrudis
Torres-Alemán, Ignacio
Santamaría Martínez, Enrique
Vicario, Carlos
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
dc.subject.none.fl_str_mv Insulin-like growth factor-I (IGF-I)
Igf-I deletion
topic Insulin-like growth factor-I (IGF-I)
Igf-I deletion
description Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of Igf-I in the nervous system (Igf-I¿/¿), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreover, Igf-I¿/¿ mice showed spatial memory deficits in the Morris water maze, and the significant sex-dependent differences displayed by Igf-ICtrl/Ctrl mice disappeared in Igf-I¿/¿ mice in the open field and rota-rod tests. Brain Igf-I deletion disorganized the granule cell layer of the dentate gyrus (DG), and it modified the relative expressions of GAD and VGLUT1, which are preferentially localized to inhibitory and excitatory presynaptic terminals. Furthermore, Igf-I deletion altered protein modules involved in receptor trafficking, synaptic proteins, and proteins that functionally interact with estrogen and androgen metabolism. Our findings indicate that brain IGF-I is crucial for long-term potentiation, and that it is involved in the regulation of spatial memory and sexual dimorphic behaviors, possibly by maintaining the granule cell layer structure and the stability of synaptic-related protein modules.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2454/46547
url https://hdl.handle.net/2454/46547
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109059RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104376RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106579RB-I00
info:eu-repo/grantAgreement/ AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BES-2017-080303
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Life Science Alliance
publisher.none.fl_str_mv Life Science Alliance
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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