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Dadun > Depósito Académico > Facultad de Ciencias > Departamento de Histología y Anatomía Patológica > DA - Ciencias - HAP - Artículos de revista >

Phenylbutyrate rescues dendritic spine loss associated with memory déficits in a Mouse modelo f Alzheimer´s disease
Authors: Ricobaraza, A. (Ana)
Cuadrado-Tejedor, M. (Mar)
Marco, S. (Sonia)
Perez-Otaño, I. (Isabel)
Garcia-Osta, A. (Ana)
Keywords: Fear memory
Histone acetylation
Chaperone
Endoplasmic reticulum stress
Dendritic spine
Issue Date: May-2010
Publisher: Wiley-Blackwell
Publisher version: http://dx.doi.org/10.1002/hipo.20883
ISSN: 1050-9631
Citation: Ricobaraza A, Cuadrado-Tejedor M, Marco S, Perez-Otano I, Garcia-Osta A. Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus 2010 Nov 10.
Abstract
Alzheimer’s disease (AD) and ageing are associated with impaired learning and memory, and recent findings point toward modulating chromatin remodeling through histone acetylation as a promising therapeutic strategy. Here we report that systemic administration of the HDAC inhibitor 4-phenylbutyrate (PBA) reinstated fear learning in the Tg2576 mouse model of AD. Tg2576 mice develop age-dependent amyloid pathology and cognitive decline that closely mimics disease progression in humans. Memory reinstatement by PBA was observed independently of the disease stage: both in 6-month-old Tg2576 mice, at the onset of the first symptoms, but also in aged, 12- to 16-month-old mice, when amyloid plaque deposition and major synaptic loss has occurred. Reversal of learning deficits was associated to a PBA-induced clearance of intraneuronal Ab accumulation, which was accompanied by mitigation of endoplasmic reticulum (ER) stress, and to restoration of dendritic spine densities of hippocampal CA1 pyramidal neurons to control levels. Furthermore, the expression of plasticity-related proteins such as the NMDA receptor subunit NR2B and the synaptic scaffold SAP102 was significantly increased by PBA. Our data suggest that the beneficial effects of PBA in memory are mediated both via its chemical chaperone- like activity and via the transcriptional activation of a cluster of proteins required for the induction of synaptic plasticity and structural remodeling.
Permanent link: http://hdl.handle.net/10171/16436
Appears in Collections:DA - CIMA - Neurociencias - Neurobiología celular - Artículos de revista
DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista
DA - Ciencias - HAP - Artículos de revista

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