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Effect of aging on 5-hydroxymethylcytosine in the mouse hippocampus

Article type: Research Article

Authors: Chen, Hu | Dzitoyeva, Svetlana | Manev, Hari

Affiliations: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

Note: [] Corresponding author: Hari Manev, MD, PhD, University of Illinois at Chicago, Psychiatric Institute, Department of Psychiatry, 1601 West Taylor Street, M/C912, Chicago, IL 60612, USA. Tel.: +1 312 996 3365; Fax: +1 312 413 4569; E-mail: [email protected]

Keywords: Epigenetic, 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-lipoxygenase (5-LOX), aging, hippocampus, ten-eleven translocation (TET)

DOI: 10.3233/RNN-2012-110223

Journal: Restorative Neurology and Neuroscience, vol. 30, no. 3, pp. 237-245, 2012

Published: 2012
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Abstract

Purpose: Aging is believed to affect epigenetic marking of brain DNA with 5-methylcytosine (5mC) and possibly via the 5mC to 5-hydroxymethylcytosine (5hmC) conversion by TET (ten-eleven translocation) enzymes. We investigated the impact of aging on hippocampal DNA 5-hydroxymethylation including in the sequence of aging-susceptible 5-lipoxygenase (5-LOX) gene. Methods: Hippocampal samples were obtained from C57BL6 mice. Cellular 5hmC localization was determined by immunofluorescence. The global 5mC and 5hmC contents were measured with the corresponding ELISA. The 5-LOX 5hmC content was measured using a glucosyltransferase/enzymatic restriction digest assay. TET mRNA was measured using qRT-PCR. Results: Global hippocampal 5hmC content increased during aging as did the 5hmC content in the 5-LOX gene. This occurred without alterations of TET1-3 mRNAs and without changes in the content of 8-hydroxy-2-deoxy-guanosine, a marker of non-enzymatic DNA oxidation. Conclusions: The aging-associated increase of hippocampal 5hmC content (global and 5-LOX) appears to be unrelated to oxidative stress. It may be driven by an altered activity but not by the increased expression of the three TET enzymes. Global 5hmC content was increased during aging in the absence of 5mC decrease, suggesting that 5hmC could act as an epigenetic marker and not only as an intermediary in DNA demethylation. Further research is needed to elucidate the functional implications of the impact of aging on hippocampal cytosine hydroxymethylation.

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