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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Neurociencias > Neurofarmacología y conducta > DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista >

Activity-regulated cytoskeleton-associated protein in rodent brain is down-regulated by high fat diet in vivo and by 27-hydroxycholesterol in vitro
Authors: Mateos, L. (Laura)
Akterin, S. (Susanne)
Gil-Bea, F. (Francisco J.)
Spulber, S. (Stefan)
Rahman, A. (Atiqur)
Björkhem, I. (Ingermar)
Schultzberg, M. (Marianne)
Flores-Morales, A. (Amílcar)
Cedazo-Minguez, A. (Ángel)
Keywords: Alzheimer’s disease
Hypercholesterolemia
Neurodegeneration
N-methyl-D-aspartate receptor activity
Src kinase
Issue Date: 2009
Publisher: Wiley Blackwell
Publisher version: http://onlinelibrary.wiley.com/doi/10.1111/j.1750-3639.2008.00174.x/abstract
ISSN: 1750-3639
Citation: Mateos L, Akterin S, Gil-Bea FJ, Spulber S, Rahman A, Bjorkhem I, et al. Activity-regulated cytoskeleton-associated protein in rodent brain is down-regulated by high fat diet in vivo and by 27-hydroxycholesterol in vitro. Brain Pathol 2009 Jan;19(1):69-80.
Abstract
Growing evidence strongly suggests that high fat diet (HFD) has an important role in some neurodegenerative disorders, including Alzheimer's disease (AD). To identify new cellular pathways linking hypercholesterolemia and neurodegeneration, we analyzed the effects of HFD on gene expression in mouse brain. Using cDNA microarrays and real time RT-PCR, we found that HFD has a mild, but significant effect on the expression of several genes. The altered genes include molecules linked to AD pathology and others of potential interest for neurodegeneration. We further investigated the effect of HFD on the activity-regulated cytoskeleton-associated protein (Arc). Expression of Arc was decreased in cerebral cortex and hippocampus of HFD-fed animals. From the known regulatory mechanisms of Arc expression, HFD reduced N-methyl-D-aspartate receptor (NMDAR) activity, as seen by decreases in tyrosine phosphorylation of NMDAR2A and levels of NMDAR1. Additionally, we demonstrated that 27-hydroxycholesterol, a cholesterol metabolite that enters the brain from the blood, decreases Arc levels as well as NMDAR and Src kinase activities in rat primary hippocampal neurons. Finally, we showed that Arc levels are decreased in the cortex of AD brains. We propose that one of the mechanisms, by which hypercholesterolemia contributes to neurodegenerative diseases, could be through Arc down-regulation caused by 27-hydroxycholesterol.
Permanent link: http://hdl.handle.net/10171/20226
Appears in Collections:DA - Farmacia - Farmacología - Artículos de revista
DA - CIMA - Neurociencias - Neurofarmacología y conducta - Artículos de Revista

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