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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/133663
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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 Técnicas2025-09-29T09:40:35Zoai: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:34982025-09-29 09:40:35.356CONICET 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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1844613284164009984 |
score |
13.070432 |