English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/150545
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

Aging Triggers a Repressive Chromatin State at Bdnf Promoters in Hippocampal Neurons

AutorPalomer, Ernest ; Martín-Segura, Adrián; Baliyan, Shishir; Ahmed, Tariq; Balschun, Detlef; Venero, César ; Martín, Mauricio G. ; Dotti, Carlos G.
Fecha de publicación13-sep-2016
EditorCell Press
CitaciónCell Reports 16: 2889- 2900 (2016)
ResumenCognitive 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.
URIhttp://hdl.handle.net/10261/150545
DOI10.1016/j.celrep.2016.08.028
Identificadoresdoi: 10.1016/j.celrep.2016.08.028
issn: 2211-1247
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
DottiCG_AgingTriggersARepressiveChromatin.pdf2,56 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.