Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior

Major depressive disorder (MDD) is a leading cause of disability worldwide, with a poorly known pathophysiology and sub-optimal treatment, based on serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. We review existing theories on MDD, paying special attention to the role played by the ventra...

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Detalhes bibliográficos
Autores: Fullana, Neus, Gasull-Camós, Júlia, Tarrés-Gatius, Mireia, Castañé, Anna, Bortolozzi, Analía, Artigas, Francesc
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2020
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/203338
Acesso em linha:http://hdl.handle.net/10261/203338
Access Level:Acceso aberto
Palavra-chave:Antidepressant effects
Astrocytes
Emotional behavior
GLAST
GLT-1
Infralimbic cortex
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
title Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
spellingShingle Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
Fullana, Neus
Antidepressant effects
Astrocytes
Emotional behavior
GLAST
GLT-1
Infralimbic cortex
title_short Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
title_full Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
title_fullStr Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
title_full_unstemmed Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
title_sort Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behavior
dc.creator.none.fl_str_mv Fullana, Neus
Gasull-Camós, Júlia
Tarrés-Gatius, Mireia
Castañé, Anna
Bortolozzi, Analía
Artigas, Francesc
author Fullana, Neus
author_facet Fullana, Neus
Gasull-Camós, Júlia
Tarrés-Gatius, Mireia
Castañé, Anna
Bortolozzi, Analía
Artigas, Francesc
author_role author
author2 Gasull-Camós, Júlia
Tarrés-Gatius, Mireia
Castañé, Anna
Bortolozzi, Analía
Artigas, Francesc
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Centro de Investigación Biomédica en Red Salud Mental (España)
Generalitat de Catalunya
Ministerio de Educación, Cultura y Deporte (España)
Artigas, Francesc [0000-0002-5880-5720]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Antidepressant effects
Astrocytes
Emotional behavior
GLAST
GLT-1
Infralimbic cortex
topic Antidepressant effects
Astrocytes
Emotional behavior
GLAST
GLT-1
Infralimbic cortex
description Major depressive disorder (MDD) is a leading cause of disability worldwide, with a poorly known pathophysiology and sub-optimal treatment, based on serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. We review existing theories on MDD, paying special attention to the role played by the ventral anterior cingulate cortex (vACC) or its rodent equivalent, infralimbic cortex (IL), which tightly control the activity of brainstem monoamine neurons (including raphe 5-HT neurons) via descending afferents. Further, astrocytes regulate excitatory synapse activity via glutamate reuptake through astrocytic transporters EAAT1 and EAAT2 (GLAST and GLT-1 in rodents), and alterations of astrocyte number/function have been reported in MDD patients and suicide victims. We recently assessed the impact of reducing GLAST/GLT-1 function in IL on emotional behavior and serotonergic function in rodents. The acute pharmacological blockade of GLT-1 with dihydrokainate (DHK) in rat IL evoked an antidepressant-like effect mediated by local AMPA-R activation and a subsequent enhancement of serotonergic function. No effects were produced by DHK microinfusion in prelimbic cortex (PrL). In the second model, a moderate small interfering RNAs (siRNA)-induced reduction of GLAST and GLT-1 expression in mouse IL markedly increased local glutamatergic neurotransmission and evoked a depressive-like phenotype (reversed by citalopram and ketamine), and reduced serotonergic function and BDNF expression in cortical/hippocampal areas. As for DHK, siRNA microinfusion in PrL did not evoke behavioral/neurochemical effects. Overall, both studies support a critical role of the astrocyte-neuron communication in the control of excitatory neurotransmission in IL, and subsequently, on emotional behavior, via the downstream associated changes on serotonergic function.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/203338
url http://hdl.handle.net/10261/203338
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#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-68346-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75797-R
https://doi.org/10.1016/j.neuropharm.2019.107914
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
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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spelling Astrocyte control of glutamatergic activity: Downstream effects on serotonergic function and emotional behaviorFullana, NeusGasull-Camós, JúliaTarrés-Gatius, MireiaCastañé, AnnaBortolozzi, AnalíaArtigas, FrancescAntidepressant effectsAstrocytesEmotional behaviorGLASTGLT-1Infralimbic cortexMajor depressive disorder (MDD) is a leading cause of disability worldwide, with a poorly known pathophysiology and sub-optimal treatment, based on serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. We review existing theories on MDD, paying special attention to the role played by the ventral anterior cingulate cortex (vACC) or its rodent equivalent, infralimbic cortex (IL), which tightly control the activity of brainstem monoamine neurons (including raphe 5-HT neurons) via descending afferents. Further, astrocytes regulate excitatory synapse activity via glutamate reuptake through astrocytic transporters EAAT1 and EAAT2 (GLAST and GLT-1 in rodents), and alterations of astrocyte number/function have been reported in MDD patients and suicide victims. We recently assessed the impact of reducing GLAST/GLT-1 function in IL on emotional behavior and serotonergic function in rodents. The acute pharmacological blockade of GLT-1 with dihydrokainate (DHK) in rat IL evoked an antidepressant-like effect mediated by local AMPA-R activation and a subsequent enhancement of serotonergic function. No effects were produced by DHK microinfusion in prelimbic cortex (PrL). In the second model, a moderate small interfering RNAs (siRNA)-induced reduction of GLAST and GLT-1 expression in mouse IL markedly increased local glutamatergic neurotransmission and evoked a depressive-like phenotype (reversed by citalopram and ketamine), and reduced serotonergic function and BDNF expression in cortical/hippocampal areas. As for DHK, siRNA microinfusion in PrL did not evoke behavioral/neurochemical effects. Overall, both studies support a critical role of the astrocyte-neuron communication in the control of excitatory neurotransmission in IL, and subsequently, on emotional behavior, via the downstream associated changes on serotonergic function.This study was supported by the Spanish Ministry of Economy and Competitiveness, SAF2015-68346-P MINECO/FEDER, UE (F.A.) and SAF2016-75797-R AEI/FEDER, UE (A.B.) co-financed by the European Regional Development Fund “A way to build Europe”. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and CERCA Programme/Generalitat de Catalunya is also acknowledged. The authors would also like to thank the support of the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2017SGR717). N.F. was a recipient of a fellowship from Spanish Ministry of Education, Culture, and Sport. J.G-C was a recipient of a fellowship from the Spanish Ministry of Economy and Competitiveness (BES-2013-063241). M.T-G was a recipient of a fellowship from Generalitat de Catalunya (2016FI_B 00285) co-financed by the European Social Fund.Peer reviewedElsevier BVMinisterio de Economía y Competitividad (España)European CommissionCentro de Investigación Biomédica en Red Salud Mental (España)Generalitat de CatalunyaMinisterio de Educación, Cultura y Deporte (España)Artigas, Francesc [0000-0002-5880-5720]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/203338reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-68346-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75797-Rhttps://doi.org/10.1016/j.neuropharm.2019.107914Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2033382026-05-22T06:33:51Z
score 15,811543

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