Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis

The mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to...

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Autores: Rodríguez-Moreno, Carla B., Cañeque-Rufo, Héctor, Flor-García, Miguel, Terreros-Roncal, Julia, Moreno-Jiménez, Elena P., Pallas-Bazarra, Noemí, Bressa, Carlo, Larrosa, Mar, Cafini, Fabio, Llorens-Martín, María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/365909
Acceso en línea:http://hdl.handle.net/10261/365909
Access Level:acceso abierto
Palabra clave:Adult hippocampal neurogenesis
Azithromycin
LPS
Retrovirus
Gut microbiome
Cytokines
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spelling Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsisRodríguez-Moreno, Carla B.Cañeque-Rufo, HéctorFlor-García, MiguelTerreros-Roncal, JuliaMoreno-Jiménez, Elena P.Pallas-Bazarra, NoemíBressa, CarloLarrosa, MarCafini, FabioLlorens-Martín, MaríaAdult hippocampal neurogenesisAzithromycinLPSRetrovirusGut microbiomeCytokinesThe mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to the cognitive reserve in aged individuals. However, the integrity of AHN is targeted by numerous pathological conditions, including neurodegenerative diseases and sustained inflammation. In this regard, the latter causes cognitive decline, mood alterations, and multiple AHN impairments. In fact, the systemic administration of Lipopolysaccharide (LPS) from E. coli to mice (a model of sepsis) triggers depression-like behavior, impairs pattern separation, and decreases the survival, maturation, and synaptic integration of adult-born hippocampal dentate granule cells. Here we tested the capacity of the macrolide antibiotic azithromycin to neutralize the deleterious consequences of LPS administration in female C57BL6J mice. This antibiotic exerted potent neuroprotective effects. It reversed the increased immobility time during the Porsolt test, hippocampal secretion of pro-inflammatory cytokines, and AHN impairments. Moreover, azithromycin promoted the synaptic integration of adult-born neurons and functionally remodeled the gut microbiome. Therefore, our data point to azithromycin as a clinically relevant drug with the putative capacity to ameliorate the negative consequences of chronic inflammation by modulating AHN and hippocampal-related behaviors.Funding for this research was provided by: CIBERNED European Research Council Universidad Autonoma de Madrid Ministerio de Economía y Competitividad Fundacion Tatiana Perez de Guzman el BuenoAcademic PressEuropean Research CouncilUniversidad Autónoma de MadridMinisterio de Economía y Competitividad (España)Fundación Tatiana Pérez de Guzmán el BuenoAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/365909reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113007RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-82185-Rinfo:eu-repo/grantAgreement/EC/ERC-CoG-2020-101001916/http://dx.doi.org/10.1016/j.bbi.2024.01.005Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3659092026-05-22T06:33:51Z
dc.title.none.fl_str_mv Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
title Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
spellingShingle Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
Rodríguez-Moreno, Carla B.
Adult hippocampal neurogenesis
Azithromycin
LPS
Retrovirus
Gut microbiome
Cytokines
title_short Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
title_full Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
title_fullStr Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
title_full_unstemmed Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
title_sort Azithromycin preserves adult hippocampal neurogenesis and behavior in a mouse model of sepsis
dc.creator.none.fl_str_mv Rodríguez-Moreno, Carla B.
Cañeque-Rufo, Héctor
Flor-García, Miguel
Terreros-Roncal, Julia
Moreno-Jiménez, Elena P.
Pallas-Bazarra, Noemí
Bressa, Carlo
Larrosa, Mar
Cafini, Fabio
Llorens-Martín, María
author Rodríguez-Moreno, Carla B.
author_facet Rodríguez-Moreno, Carla B.
Cañeque-Rufo, Héctor
Flor-García, Miguel
Terreros-Roncal, Julia
Moreno-Jiménez, Elena P.
Pallas-Bazarra, Noemí
Bressa, Carlo
Larrosa, Mar
Cafini, Fabio
Llorens-Martín, María
author_role author
author2 Cañeque-Rufo, Héctor
Flor-García, Miguel
Terreros-Roncal, Julia
Moreno-Jiménez, Elena P.
Pallas-Bazarra, Noemí
Bressa, Carlo
Larrosa, Mar
Cafini, Fabio
Llorens-Martín, María
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Research Council
Universidad Autónoma de Madrid
Ministerio de Economía y Competitividad (España)
Fundación Tatiana Pérez de Guzmán el Bueno
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Adult hippocampal neurogenesis
Azithromycin
LPS
Retrovirus
Gut microbiome
Cytokines
topic Adult hippocampal neurogenesis
Azithromycin
LPS
Retrovirus
Gut microbiome
Cytokines
description The mammalian hippocampus can generate new neurons throughout life. Known as adult hippocampal neurogenesis (AHN), this process participates in learning, memory, mood regulation, and forgetting. The continuous incorporation of new neurons enhances the plasticity of the hippocampus and contributes to the cognitive reserve in aged individuals. However, the integrity of AHN is targeted by numerous pathological conditions, including neurodegenerative diseases and sustained inflammation. In this regard, the latter causes cognitive decline, mood alterations, and multiple AHN impairments. In fact, the systemic administration of Lipopolysaccharide (LPS) from E. coli to mice (a model of sepsis) triggers depression-like behavior, impairs pattern separation, and decreases the survival, maturation, and synaptic integration of adult-born hippocampal dentate granule cells. Here we tested the capacity of the macrolide antibiotic azithromycin to neutralize the deleterious consequences of LPS administration in female C57BL6J mice. This antibiotic exerted potent neuroprotective effects. It reversed the increased immobility time during the Porsolt test, hippocampal secretion of pro-inflammatory cytokines, and AHN impairments. Moreover, azithromycin promoted the synaptic integration of adult-born neurons and functionally remodeled the gut microbiome. Therefore, our data point to azithromycin as a clinically relevant drug with the putative capacity to ameliorate the negative consequences of chronic inflammation by modulating AHN and hippocampal-related behaviors.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/365909
url http://hdl.handle.net/10261/365909
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113007RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-82185-R
info:eu-repo/grantAgreement/EC/ERC-CoG-2020-101001916/
http://dx.doi.org/10.1016/j.bbi.2024.01.005
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Academic Press
publisher.none.fl_str_mv Academic Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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