Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons

Autores
Palomer, Ernest; Martín, Mauricio Gerardo; Baliyan, Shishir; Ahmed, Tariq; Balschun, Detlef; Venero, Cesar; Martín, Mauricio Gerardo; Dotti, Carlos G.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated activation of CaMKII. Decreased NMDAR signaling prevents changes associated with activation at specific Bdnf promoters, including displacement of histone deacetylase 4, recruitment of the histone acetyltransferase CBP, increased H3K27 acetylation, and reduced H3K27 trimethylation. The decrease in NMDA-CaMKII signaling arises from constitutive reduction of synaptic cholesterol that occurs with normal aging. Increasing the levels of neuronal cholesterol in aged neurons in vitro, ex vivo, and in vivo restored NMDA-induced Bdnf expression and chromatin remodeling. Furthermore, pharmacological prevention of age-associated cholesterol reduction rescued signaling and cognitive deficits of aged mice. Thus, reducing hippocampal cholesterol loss may represent a therapeutic approach to reverse cognitive decline during aging.
Fil: Palomer, Ernest. Universidad Autonoma de Madrid. Centro de Biología Molecular; España
Fil: Martín, Mauricio Gerardo. Universidad Autonoma de Madrid. Centro de Biología Molecular; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Baliyan, Shishir. Universidad Nacional de Educación a Distancia; España
Fil: Ahmed, Tariq. Katholikie Universiteit Leuven; Bélgica
Fil: Balschun, Detlef. Katholikie Universiteit Leuven; Bélgica
Fil: Venero, Cesar. Universidad Nacional de Educación a Distancia; España
Fil: Martín, Mauricio Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Autonoma de Madrid. Centro de Biología Molecular; España
Fil: Dotti, Carlos G.. Universidad Autonoma de Madrid. Centro de Biología Molecular; España
Materia
AGING
EPIGENETIC
MEMORY
CHOLESTEROL
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:11336/75609
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/75609
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neuronsPalomer, ErnestMartín, Mauricio GerardoBaliyan, ShishirAhmed, TariqBalschun, DetlefVenero, CesarMartín, Mauricio GerardoDotti, Carlos G.AGINGEPIGENETICMEMORYCHOLESTEROLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated activation of CaMKII. Decreased NMDAR signaling prevents changes associated with activation at specific Bdnf promoters, including displacement of histone deacetylase 4, recruitment of the histone acetyltransferase CBP, increased H3K27 acetylation, and reduced H3K27 trimethylation. The decrease in NMDA-CaMKII signaling arises from constitutive reduction of synaptic cholesterol that occurs with normal aging. Increasing the levels of neuronal cholesterol in aged neurons in vitro, ex vivo, and in vivo restored NMDA-induced Bdnf expression and chromatin remodeling. Furthermore, pharmacological prevention of age-associated cholesterol reduction rescued signaling and cognitive deficits of aged mice. Thus, reducing hippocampal cholesterol loss may represent a therapeutic approach to reverse cognitive decline during aging.Fil: Palomer, Ernest. Universidad Autonoma de Madrid. Centro de Biología Molecular; EspañaFil: Martín, Mauricio Gerardo. Universidad Autonoma de Madrid. Centro de Biología Molecular; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Baliyan, Shishir. Universidad Nacional de Educación a Distancia; EspañaFil: Ahmed, Tariq. Katholikie Universiteit Leuven; BélgicaFil: Balschun, Detlef. Katholikie Universiteit Leuven; BélgicaFil: Venero, Cesar. Universidad Nacional de Educación a Distancia; EspañaFil: Martín, Mauricio Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Autonoma de Madrid. Centro de Biología Molecular; EspañaFil: Dotti, Carlos G.. Universidad Autonoma de Madrid. Centro de Biología Molecular; EspañaElsevier B.V.2016-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/75609Palomer, Ernest; Martín, Mauricio Gerardo; Baliyan, Shishir; Ahmed, Tariq; Balschun, Detlef; et al.; Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons; Elsevier B.V.; Cell Reports; 16; 11; 9-2016; 2889-29002211-12472211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.08.028info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124716310920info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:05:10Zoai:ri.conicet.gov.ar:11336/75609instacron: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 13:05:10.999CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
title Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
spellingShingle Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
Palomer, Ernest
AGING
EPIGENETIC
MEMORY
CHOLESTEROL
title_short Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
title_full Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
title_fullStr Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
title_full_unstemmed Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
title_sort Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons
dc.creator.none.fl_str_mv Palomer, Ernest
Martín, Mauricio Gerardo
Baliyan, Shishir
Ahmed, Tariq
Balschun, Detlef
Venero, Cesar
Martín, Mauricio Gerardo
Dotti, Carlos G.
author Palomer, Ernest
author_facet Palomer, Ernest
Martín, Mauricio Gerardo
Baliyan, Shishir
Ahmed, Tariq
Balschun, Detlef
Venero, Cesar
Dotti, Carlos G.
author_role author
author2 Martín, Mauricio Gerardo
Baliyan, Shishir
Ahmed, Tariq
Balschun, Detlef
Venero, Cesar
Dotti, Carlos G.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv AGING
EPIGENETIC
MEMORY
CHOLESTEROL
topic AGING
EPIGENETIC
MEMORY
CHOLESTEROL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated activation of CaMKII. Decreased NMDAR signaling prevents changes associated with activation at specific Bdnf promoters, including displacement of histone deacetylase 4, recruitment of the histone acetyltransferase CBP, increased H3K27 acetylation, and reduced H3K27 trimethylation. The decrease in NMDA-CaMKII signaling arises from constitutive reduction of synaptic cholesterol that occurs with normal aging. Increasing the levels of neuronal cholesterol in aged neurons in vitro, ex vivo, and in vivo restored NMDA-induced Bdnf expression and chromatin remodeling. Furthermore, pharmacological prevention of age-associated cholesterol reduction rescued signaling and cognitive deficits of aged mice. Thus, reducing hippocampal cholesterol loss may represent a therapeutic approach to reverse cognitive decline during aging.
Fil: Palomer, Ernest. Universidad Autonoma de Madrid. Centro de Biología Molecular; España
Fil: Martín, Mauricio Gerardo. Universidad Autonoma de Madrid. Centro de Biología Molecular; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Baliyan, Shishir. Universidad Nacional de Educación a Distancia; España
Fil: Ahmed, Tariq. Katholikie Universiteit Leuven; Bélgica
Fil: Balschun, Detlef. Katholikie Universiteit Leuven; Bélgica
Fil: Venero, Cesar. Universidad Nacional de Educación a Distancia; España
Fil: Martín, Mauricio Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Autonoma de Madrid. Centro de Biología Molecular; España
Fil: Dotti, Carlos G.. Universidad Autonoma de Madrid. Centro de Biología Molecular; España
description Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated activation of CaMKII. Decreased NMDAR signaling prevents changes associated with activation at specific Bdnf promoters, including displacement of histone deacetylase 4, recruitment of the histone acetyltransferase CBP, increased H3K27 acetylation, and reduced H3K27 trimethylation. The decrease in NMDA-CaMKII signaling arises from constitutive reduction of synaptic cholesterol that occurs with normal aging. Increasing the levels of neuronal cholesterol in aged neurons in vitro, ex vivo, and in vivo restored NMDA-induced Bdnf expression and chromatin remodeling. Furthermore, pharmacological prevention of age-associated cholesterol reduction rescued signaling and cognitive deficits of aged mice. Thus, reducing hippocampal cholesterol loss may represent a therapeutic approach to reverse cognitive decline during aging.
publishDate 2016
dc.date.none.fl_str_mv 2016-09
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/11336/75609
Palomer, Ernest; Martín, Mauricio Gerardo; Baliyan, Shishir; Ahmed, Tariq; Balschun, Detlef; et al.; Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons; Elsevier B.V.; Cell Reports; 16; 11; 9-2016; 2889-2900
2211-1247
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/75609
identifier_str_mv Palomer, Ernest; Martín, Mauricio Gerardo; Baliyan, Shishir; Ahmed, Tariq; Balschun, Detlef; et al.; Aging triggers a repressive chromatin state at Bdnf promoters in hippocampal neurons; Elsevier B.V.; Cell Reports; 16; 11; 9-2016; 2889-2900
2211-1247
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.08.028
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124716310920
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 Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
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
_version_ 1842980183140728832
score 12.993085

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