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Title of Journal: J Mol Neurosci

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Abbravation: Journal of Molecular Neuroscience

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Springer US

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DOI

10.1002/div.5567

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1559-1166

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Liver X Receptor Agonist Modifies the DNA Methylat

Authors: A G SandovalHernández H G Hernández A Restrepo J I Muñoz G F Bayon A F Fernández M F Fraga G P CardonaGómez H Arboleda Gonzalo H Arboleda
Publish Date: 2015/11/09
Volume: 58, Issue: 2, Pages: 243-253
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Abstract

The liver X receptor agonist GW3965 improves cognition in Alzheimer’s disease AD mouse models Here we determined if shortterm GW3965 treatment induces changes in the DNA methylation state of the hippocampus which are associated with cognitive improvement Twentyfourmonthold tripletransgenic AD 3xTgAD 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 13715 interrogated probes in treated 3xTgAD mice compared with untreated 3xTgAD mice These changes in methylation probes include 29 gene loci Importantly changes in methylation status were mainly from synapserelated genes SYP SYN1 and DLG3 and neurogenesisassociated 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 GW3965Animals were handled following the Colombian Law 84 of 1989 and Resolution 8430 of 1993 and international regulations and standards on animal welfare and conformed to the Animal Research Reporting In Vivo Experiments ARRIVE guidelines Kilkenny et al 2010

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