| Literature DB >> 26553261 |
A G Sandoval-Hernández1, H G Hernández2, A Restrepo1, J I Muñoz3, G F Bayon4, A F Fernández4, M F Fraga4, G P Cardona-Gómez3, H Arboleda2, Gonzalo H Arboleda5,6.
Abstract
The liver X receptor agonist, GW3965, improves cognition in Alzheimer's disease (AD) mouse models. Here, we determined if short-term GW3965 treatment induces changes in the DNA methylation state of the hippocampus, which are associated with cognitive improvement. Twenty-four-month-old triple-transgenic AD (3xTg-AD) mice were treated with GW3965 (50 mg/kg/day for 6 days). DNA methylation state was examined by modified bisulfite conversion and hybridization on Illumina Infinium Methylation BeadChip 450 k arrays. The Morris water maze was used for behavioral analysis. Our results show in addition to improvement in cognition methylation changes in 39 of 13,715 interrogated probes in treated 3xTg-AD mice compared with untreated 3xTg-AD mice. These changes in methylation probes include 29 gene loci. Importantly, changes in methylation status were mainly from synapse-related genes (SYP, SYN1, and DLG3) and neurogenesis-associated genes (HMGB3 and RBBP7). Thus, our results indicate that liver X receptors (LXR) agonist treatment induces rapid changes in DNA methylation, particularly in loci associated with genes involved in neurogenesis and synaptic function. Our results suggest a new potential mechanism to explain the beneficial effect of GW3965.Entities:
Keywords: Alzheimer’s disease; GW3965; Liver X receptors; Triple transgenic mice
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Year: 2015 PMID： 26553261 DOI： 10.1007/s12031-015-0665-8
Source DB: PubMed Journal: J Mol Neurosci ISSN： 0895-8696 Impact factor: 3.444