Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin

Autores
Diaz, Silvina Laura; Narboux Nême, Nicolas; Trowbridge, Sara; Scotto Lomassese, Sophie; Kleine Borgemann, Felix B.; Jessberger, Sebastian; Giros, Bruno; Maroteaux, Luc; Deneris, Evan; Gaspar, Patricia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Increased adult neurogenesis is a major neurobiological correlate of the beneficial effects of antidepressants. Indeed, selective serotonin (5-HT) re-uptake inhibitors, which increase 5-HT transmission, enhance adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, the consequences of 5-HT depletion are still unclear as studies using neurotoxins that target serotonergic neurons reached contradictory conclusions on the role of 5-HT on DG cell proliferation. Here, we analysed two genetic models of 5-HT depletion, the Pet1-/- and the VMAT2f/f; SERTcre/+ mice, which have, respectively, 80 and 95% reductions in hippocampal 5-HT. In both models, we found unchanged cell proliferation of the neural precursors in the DG subgranular zone, whereas a significant increase in the survival of newborn neurons was noted 1 and 4 weeks after BrdU injections. This pro-survival trait was phenocopied pharmacologically with 5-HT synthesis inhibitor PCPA treatment in adults, indicating that this effect was not developmental. Furthermore, a 1-week administration of the 5-HT1A receptor agonist 8-OH-DPAT in Pet1-/- and PCPA-treated mice normalised hippocampal cell survival. Overall, our results indicate that constitutive 5-HT depletion does not alter the proliferation of neural precursors in the DG but promotes the survival of newborn cells, an effect which involves activation of postsynaptic 5-HT1A receptors. The role of 5-HT in selective neuronal elimination points to a new facet in its multiple effects in controlling neural circuit maturation.
Fil: Diaz, Silvina Laura. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina
Fil: Narboux Nême, Nicolas. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Trowbridge, Sara. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Scotto Lomassese, Sophie. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Kleine Borgemann, Felix B.. Universitat Zurich; Suiza
Fil: Jessberger, Sebastian. Universitat Zurich; Suiza
Fil: Giros, Bruno. Universite Pierre Et Marie Curie; Francia. Centre National de la Recherche Scientifique; Francia. Mc Gill University; Canadá
Fil: Maroteaux, Luc. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Deneris, Evan. Case Western Reserve University; Estados Unidos
Fil: Gaspar, Patricia. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Materia
5-Hydroxytryptamine Depletion
Adult Neurogenesis
Genetic Mouse Models
Hippocampus
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:11336/12161
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/12161
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotoninDiaz, Silvina LauraNarboux Nême, NicolasTrowbridge, SaraScotto Lomassese, SophieKleine Borgemann, Felix B.Jessberger, SebastianGiros, BrunoMaroteaux, LucDeneris, EvanGaspar, Patricia5-Hydroxytryptamine DepletionAdult NeurogenesisGenetic Mouse ModelsHippocampushttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Increased adult neurogenesis is a major neurobiological correlate of the beneficial effects of antidepressants. Indeed, selective serotonin (5-HT) re-uptake inhibitors, which increase 5-HT transmission, enhance adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, the consequences of 5-HT depletion are still unclear as studies using neurotoxins that target serotonergic neurons reached contradictory conclusions on the role of 5-HT on DG cell proliferation. Here, we analysed two genetic models of 5-HT depletion, the Pet1-/- and the VMAT2f/f; SERTcre/+ mice, which have, respectively, 80 and 95% reductions in hippocampal 5-HT. In both models, we found unchanged cell proliferation of the neural precursors in the DG subgranular zone, whereas a significant increase in the survival of newborn neurons was noted 1 and 4 weeks after BrdU injections. This pro-survival trait was phenocopied pharmacologically with 5-HT synthesis inhibitor PCPA treatment in adults, indicating that this effect was not developmental. Furthermore, a 1-week administration of the 5-HT1A receptor agonist 8-OH-DPAT in Pet1-/- and PCPA-treated mice normalised hippocampal cell survival. Overall, our results indicate that constitutive 5-HT depletion does not alter the proliferation of neural precursors in the DG but promotes the survival of newborn cells, an effect which involves activation of postsynaptic 5-HT1A receptors. The role of 5-HT in selective neuronal elimination points to a new facet in its multiple effects in controlling neural circuit maturation.Fil: Diaz, Silvina Laura. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; ArgentinaFil: Narboux Nême, Nicolas. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; FranciaFil: Trowbridge, Sara. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; FranciaFil: Scotto Lomassese, Sophie. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; FranciaFil: Kleine Borgemann, Felix B.. Universitat Zurich; SuizaFil: Jessberger, Sebastian. Universitat Zurich; SuizaFil: Giros, Bruno. Universite Pierre Et Marie Curie; Francia. Centre National de la Recherche Scientifique; Francia. Mc Gill University; CanadáFil: Maroteaux, Luc. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; FranciaFil: Deneris, Evan. Case Western Reserve University; Estados UnidosFil: Gaspar, Patricia. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; FranciaWiley2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12161Diaz, Silvina Laura; Narboux Nême, Nicolas; Trowbridge, Sara; Scotto Lomassese, Sophie; Kleine Borgemann, Felix B.; et al.; Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin; Wiley; European Journal Of Neuroscience; 38; 5; 9-2013; 2650-26580953-816Xenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/ejn.12297/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/ejn.12297info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:26Zoai:ri.conicet.gov.ar:11336/12161instacron: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 13:09:27.154CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
title Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
spellingShingle Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
Diaz, Silvina Laura
5-Hydroxytryptamine Depletion
Adult Neurogenesis
Genetic Mouse Models
Hippocampus
title_short Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
title_full Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
title_fullStr Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
title_full_unstemmed Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
title_sort Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin
dc.creator.none.fl_str_mv Diaz, Silvina Laura
Narboux Nême, Nicolas
Trowbridge, Sara
Scotto Lomassese, Sophie
Kleine Borgemann, Felix B.
Jessberger, Sebastian
Giros, Bruno
Maroteaux, Luc
Deneris, Evan
Gaspar, Patricia
author Diaz, Silvina Laura
author_facet Diaz, Silvina Laura
Narboux Nême, Nicolas
Trowbridge, Sara
Scotto Lomassese, Sophie
Kleine Borgemann, Felix B.
Jessberger, Sebastian
Giros, Bruno
Maroteaux, Luc
Deneris, Evan
Gaspar, Patricia
author_role author
author2 Narboux Nême, Nicolas
Trowbridge, Sara
Scotto Lomassese, Sophie
Kleine Borgemann, Felix B.
Jessberger, Sebastian
Giros, Bruno
Maroteaux, Luc
Deneris, Evan
Gaspar, Patricia
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 5-Hydroxytryptamine Depletion
Adult Neurogenesis
Genetic Mouse Models
Hippocampus
topic 5-Hydroxytryptamine Depletion
Adult Neurogenesis
Genetic Mouse Models
Hippocampus
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Increased adult neurogenesis is a major neurobiological correlate of the beneficial effects of antidepressants. Indeed, selective serotonin (5-HT) re-uptake inhibitors, which increase 5-HT transmission, enhance adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, the consequences of 5-HT depletion are still unclear as studies using neurotoxins that target serotonergic neurons reached contradictory conclusions on the role of 5-HT on DG cell proliferation. Here, we analysed two genetic models of 5-HT depletion, the Pet1-/- and the VMAT2f/f; SERTcre/+ mice, which have, respectively, 80 and 95% reductions in hippocampal 5-HT. In both models, we found unchanged cell proliferation of the neural precursors in the DG subgranular zone, whereas a significant increase in the survival of newborn neurons was noted 1 and 4 weeks after BrdU injections. This pro-survival trait was phenocopied pharmacologically with 5-HT synthesis inhibitor PCPA treatment in adults, indicating that this effect was not developmental. Furthermore, a 1-week administration of the 5-HT1A receptor agonist 8-OH-DPAT in Pet1-/- and PCPA-treated mice normalised hippocampal cell survival. Overall, our results indicate that constitutive 5-HT depletion does not alter the proliferation of neural precursors in the DG but promotes the survival of newborn cells, an effect which involves activation of postsynaptic 5-HT1A receptors. The role of 5-HT in selective neuronal elimination points to a new facet in its multiple effects in controlling neural circuit maturation.
Fil: Diaz, Silvina Laura. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias "Profesor Eduardo de Robertis"; Argentina
Fil: Narboux Nême, Nicolas. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Trowbridge, Sara. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Scotto Lomassese, Sophie. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Kleine Borgemann, Felix B.. Universitat Zurich; Suiza
Fil: Jessberger, Sebastian. Universitat Zurich; Suiza
Fil: Giros, Bruno. Universite Pierre Et Marie Curie; Francia. Centre National de la Recherche Scientifique; Francia. Mc Gill University; Canadá
Fil: Maroteaux, Luc. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
Fil: Deneris, Evan. Case Western Reserve University; Estados Unidos
Fil: Gaspar, Patricia. Inserm; Francia. Universite Pierre et Marie Curie; Francia. Institut du Fer à Moulin; Francia
description Increased adult neurogenesis is a major neurobiological correlate of the beneficial effects of antidepressants. Indeed, selective serotonin (5-HT) re-uptake inhibitors, which increase 5-HT transmission, enhance adult neurogenesis in the dentate gyrus (DG) of the hippocampus. However, the consequences of 5-HT depletion are still unclear as studies using neurotoxins that target serotonergic neurons reached contradictory conclusions on the role of 5-HT on DG cell proliferation. Here, we analysed two genetic models of 5-HT depletion, the Pet1-/- and the VMAT2f/f; SERTcre/+ mice, which have, respectively, 80 and 95% reductions in hippocampal 5-HT. In both models, we found unchanged cell proliferation of the neural precursors in the DG subgranular zone, whereas a significant increase in the survival of newborn neurons was noted 1 and 4 weeks after BrdU injections. This pro-survival trait was phenocopied pharmacologically with 5-HT synthesis inhibitor PCPA treatment in adults, indicating that this effect was not developmental. Furthermore, a 1-week administration of the 5-HT1A receptor agonist 8-OH-DPAT in Pet1-/- and PCPA-treated mice normalised hippocampal cell survival. Overall, our results indicate that constitutive 5-HT depletion does not alter the proliferation of neural precursors in the DG but promotes the survival of newborn cells, an effect which involves activation of postsynaptic 5-HT1A receptors. The role of 5-HT in selective neuronal elimination points to a new facet in its multiple effects in controlling neural circuit maturation.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
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/11336/12161
Diaz, Silvina Laura; Narboux Nême, Nicolas; Trowbridge, Sara; Scotto Lomassese, Sophie; Kleine Borgemann, Felix B.; et al.; Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin; Wiley; European Journal Of Neuroscience; 38; 5; 9-2013; 2650-2658
0953-816X
url http://hdl.handle.net/11336/12161
identifier_str_mv Diaz, Silvina Laura; Narboux Nême, Nicolas; Trowbridge, Sara; Scotto Lomassese, Sophie; Kleine Borgemann, Felix B.; et al.; Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin; Wiley; European Journal Of Neuroscience; 38; 5; 9-2013; 2650-2658
0953-816X
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/ejn.12297/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/ejn.12297
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
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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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