Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia

Autores
Terreros Roncal, Julia; Flor García, Miguel; Moreno Jiménez, Elena P.; Pallas Bazarra, Noemí; Rábano, Alberto; Sah, Nirnath; Van Praag, Henriette; Giacomini, Damiana Paula; Schinder, Alejandro Fabián; Ávila, Jesús; Llorens Martín, Maria
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Frontotemporal dementia (FTD) is characterized by neuronal loss in the frontal and temporal lobes of the brain. Here, we provide the first evidence of striking morphological alterations in dentate granule cells (DGCs) of FTD patients and in a mouse model of the disease, Tau VLW mice. Taking advantage of the fact that the hippocampal dentate gyrus (DG) gives rise to newborn DGCs throughout the lifetime in rodents, we used RGB retroviruses to study the temporary course of these alterations in newborn DGCs of female Tau VLW mice. In addition, retroviruses that encode either PSD95:GFP or Syn:GFP revealed striking alterations in the afferent and efferent connectivity of newborn Tau VLW DGCs, and monosynaptic retrograde rabies virus tracing showed that these cells are disconnected from distal brain regions and local sources of excitatory innervation. However, the same cells exhibited a predominance of local inhibitory innervation. Accordingly, the expression of presynaptic and postsynaptic markers of inhibitory synapses was markedly increased in the DG of Tau VLW mice and FTD patients. Moreover, an increased number of neuropeptide Y-positive interneurons in the DG correlated with a reduced number of activated egr-1 + DGCs in Tau VLW mice. Finally, we tested the therapeutic potential of environmental enrichment and chemoactivation to reverse these alterations in mice. Both strategies reversed the morphological alterations of newborn DGCs and partially restored their connectivity in a mouse model of the disease. Moreover, our data point to remarkable morphological similarities between the DGCs of Tau VLW mice and FTD patients.
Fil: Terreros Roncal, Julia. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Flor García, Miguel. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Moreno Jiménez, Elena P.. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Pallas Bazarra, Noemí. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Rábano, Alberto. No especifíca;
Fil: Sah, Nirnath. National Institutes of Health; Estados Unidos
Fil: Van Praag, Henriette. National Institutes of Health; Estados Unidos
Fil: Giacomini, Damiana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Schinder, Alejandro Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ávila, Jesús. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Llorens Martín, Maria. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Materia
DENTATE GRANULE CELLS (DGCS)
DREADD
ENVIRONMENTAL ENRICHMENT
FRONTOTEMPORAL DEMENTIA (FTD)
RABIES VIRUS
RGB RETROVIRUS
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:11336/133663
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/133663
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal DementiaTerreros Roncal, JuliaFlor García, MiguelMoreno Jiménez, Elena P.Pallas Bazarra, NoemíRábano, AlbertoSah, NirnathVan Praag, HenrietteGiacomini, Damiana PaulaSchinder, Alejandro FabiánÁvila, JesúsLlorens Martín, MariaDENTATE GRANULE CELLS (DGCS)DREADDENVIRONMENTAL ENRICHMENTFRONTOTEMPORAL DEMENTIA (FTD)RABIES VIRUSRGB RETROVIRUShttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Frontotemporal dementia (FTD) is characterized by neuronal loss in the frontal and temporal lobes of the brain. Here, we provide the first evidence of striking morphological alterations in dentate granule cells (DGCs) of FTD patients and in a mouse model of the disease, Tau VLW mice. Taking advantage of the fact that the hippocampal dentate gyrus (DG) gives rise to newborn DGCs throughout the lifetime in rodents, we used RGB retroviruses to study the temporary course of these alterations in newborn DGCs of female Tau VLW mice. In addition, retroviruses that encode either PSD95:GFP or Syn:GFP revealed striking alterations in the afferent and efferent connectivity of newborn Tau VLW DGCs, and monosynaptic retrograde rabies virus tracing showed that these cells are disconnected from distal brain regions and local sources of excitatory innervation. However, the same cells exhibited a predominance of local inhibitory innervation. Accordingly, the expression of presynaptic and postsynaptic markers of inhibitory synapses was markedly increased in the DG of Tau VLW mice and FTD patients. Moreover, an increased number of neuropeptide Y-positive interneurons in the DG correlated with a reduced number of activated egr-1 + DGCs in Tau VLW mice. Finally, we tested the therapeutic potential of environmental enrichment and chemoactivation to reverse these alterations in mice. Both strategies reversed the morphological alterations of newborn DGCs and partially restored their connectivity in a mouse model of the disease. Moreover, our data point to remarkable morphological similarities between the DGCs of Tau VLW mice and FTD patients.Fil: Terreros Roncal, Julia. Universidad Autónoma de Madrid. Facultad de Ciencias; EspañaFil: Flor García, Miguel. Universidad Autónoma de Madrid. Facultad de Ciencias; EspañaFil: Moreno Jiménez, Elena P.. Universidad Autónoma de Madrid. Facultad de Ciencias; EspañaFil: Pallas Bazarra, Noemí. Universidad Autónoma de Madrid. Facultad de Ciencias; EspañaFil: Rábano, Alberto. No especifíca;Fil: Sah, Nirnath. National Institutes of Health; Estados UnidosFil: Van Praag, Henriette. National Institutes of Health; Estados UnidosFil: Giacomini, Damiana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Schinder, Alejandro Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ávila, Jesús. Universidad Autónoma de Madrid. Facultad de Ciencias; EspañaFil: Llorens Martín, Maria. Universidad Autónoma de Madrid. Facultad de Ciencias; EspañaSociety for Neuroscience2019-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/133663Terreros Roncal, Julia; Flor García, Miguel; Moreno Jiménez, Elena P.; Pallas Bazarra, Noemí; Rábano, Alberto; et al.; Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia; Society for Neuroscience; Journal of Neuroscience; 39; 29; 5-2019; 5794-58150270-64741529-2401CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2724-18.2019info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/39/29/5794.longinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:09:13Zoai:ri.conicet.gov.ar:11336/133663instacron: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:34982025-10-22 11:09:13.898CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
title Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
spellingShingle Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
Terreros Roncal, Julia
DENTATE GRANULE CELLS (DGCS)
DREADD
ENVIRONMENTAL ENRICHMENT
FRONTOTEMPORAL DEMENTIA (FTD)
RABIES VIRUS
RGB RETROVIRUS
title_short Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
title_full Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
title_fullStr Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
title_full_unstemmed Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
title_sort Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia
dc.creator.none.fl_str_mv Terreros Roncal, Julia
Flor García, Miguel
Moreno Jiménez, Elena P.
Pallas Bazarra, Noemí
Rábano, Alberto
Sah, Nirnath
Van Praag, Henriette
Giacomini, Damiana Paula
Schinder, Alejandro Fabián
Ávila, Jesús
Llorens Martín, Maria
author Terreros Roncal, Julia
author_facet Terreros Roncal, Julia
Flor García, Miguel
Moreno Jiménez, Elena P.
Pallas Bazarra, Noemí
Rábano, Alberto
Sah, Nirnath
Van Praag, Henriette
Giacomini, Damiana Paula
Schinder, Alejandro Fabián
Ávila, Jesús
Llorens Martín, Maria
author_role author
author2 Flor García, Miguel
Moreno Jiménez, Elena P.
Pallas Bazarra, Noemí
Rábano, Alberto
Sah, Nirnath
Van Praag, Henriette
Giacomini, Damiana Paula
Schinder, Alejandro Fabián
Ávila, Jesús
Llorens Martín, Maria
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DENTATE GRANULE CELLS (DGCS)
DREADD
ENVIRONMENTAL ENRICHMENT
FRONTOTEMPORAL DEMENTIA (FTD)
RABIES VIRUS
RGB RETROVIRUS
topic DENTATE GRANULE CELLS (DGCS)
DREADD
ENVIRONMENTAL ENRICHMENT
FRONTOTEMPORAL DEMENTIA (FTD)
RABIES VIRUS
RGB RETROVIRUS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Frontotemporal dementia (FTD) is characterized by neuronal loss in the frontal and temporal lobes of the brain. Here, we provide the first evidence of striking morphological alterations in dentate granule cells (DGCs) of FTD patients and in a mouse model of the disease, Tau VLW mice. Taking advantage of the fact that the hippocampal dentate gyrus (DG) gives rise to newborn DGCs throughout the lifetime in rodents, we used RGB retroviruses to study the temporary course of these alterations in newborn DGCs of female Tau VLW mice. In addition, retroviruses that encode either PSD95:GFP or Syn:GFP revealed striking alterations in the afferent and efferent connectivity of newborn Tau VLW DGCs, and monosynaptic retrograde rabies virus tracing showed that these cells are disconnected from distal brain regions and local sources of excitatory innervation. However, the same cells exhibited a predominance of local inhibitory innervation. Accordingly, the expression of presynaptic and postsynaptic markers of inhibitory synapses was markedly increased in the DG of Tau VLW mice and FTD patients. Moreover, an increased number of neuropeptide Y-positive interneurons in the DG correlated with a reduced number of activated egr-1 + DGCs in Tau VLW mice. Finally, we tested the therapeutic potential of environmental enrichment and chemoactivation to reverse these alterations in mice. Both strategies reversed the morphological alterations of newborn DGCs and partially restored their connectivity in a mouse model of the disease. Moreover, our data point to remarkable morphological similarities between the DGCs of Tau VLW mice and FTD patients.
Fil: Terreros Roncal, Julia. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Flor García, Miguel. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Moreno Jiménez, Elena P.. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Pallas Bazarra, Noemí. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Rábano, Alberto. No especifíca;
Fil: Sah, Nirnath. National Institutes of Health; Estados Unidos
Fil: Van Praag, Henriette. National Institutes of Health; Estados Unidos
Fil: Giacomini, Damiana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Schinder, Alejandro Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ávila, Jesús. Universidad Autónoma de Madrid. Facultad de Ciencias; España
Fil: Llorens Martín, Maria. Universidad Autónoma de Madrid. Facultad de Ciencias; España
description Frontotemporal dementia (FTD) is characterized by neuronal loss in the frontal and temporal lobes of the brain. Here, we provide the first evidence of striking morphological alterations in dentate granule cells (DGCs) of FTD patients and in a mouse model of the disease, Tau VLW mice. Taking advantage of the fact that the hippocampal dentate gyrus (DG) gives rise to newborn DGCs throughout the lifetime in rodents, we used RGB retroviruses to study the temporary course of these alterations in newborn DGCs of female Tau VLW mice. In addition, retroviruses that encode either PSD95:GFP or Syn:GFP revealed striking alterations in the afferent and efferent connectivity of newborn Tau VLW DGCs, and monosynaptic retrograde rabies virus tracing showed that these cells are disconnected from distal brain regions and local sources of excitatory innervation. However, the same cells exhibited a predominance of local inhibitory innervation. Accordingly, the expression of presynaptic and postsynaptic markers of inhibitory synapses was markedly increased in the DG of Tau VLW mice and FTD patients. Moreover, an increased number of neuropeptide Y-positive interneurons in the DG correlated with a reduced number of activated egr-1 + DGCs in Tau VLW mice. Finally, we tested the therapeutic potential of environmental enrichment and chemoactivation to reverse these alterations in mice. Both strategies reversed the morphological alterations of newborn DGCs and partially restored their connectivity in a mouse model of the disease. Moreover, our data point to remarkable morphological similarities between the DGCs of Tau VLW mice and FTD patients.
publishDate 2019
dc.date.none.fl_str_mv 2019-05
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/11336/133663
Terreros Roncal, Julia; Flor García, Miguel; Moreno Jiménez, Elena P.; Pallas Bazarra, Noemí; Rábano, Alberto; et al.; Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia; Society for Neuroscience; Journal of Neuroscience; 39; 29; 5-2019; 5794-5815
0270-6474
1529-2401
CONICET Digital
CONICET
url http://hdl.handle.net/11336/133663
identifier_str_mv Terreros Roncal, Julia; Flor García, Miguel; Moreno Jiménez, Elena P.; Pallas Bazarra, Noemí; Rábano, Alberto; et al.; Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia; Society for Neuroscience; Journal of Neuroscience; 39; 29; 5-2019; 5794-5815
0270-6474
1529-2401
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.2724-18.2019
info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/39/29/5794.long
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 Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
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 12.982451

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