Age-related disturbances in DNA (hydroxy)methylation in APP/PS1 mice

Leonidas Chouliaras, Roy Lardenoije, Gunter Kenis, DIego Mastroeni, Patrick R. Hof, Jim Van Os, Harry W.M. Steinbusch, Fred W. Van Leeuwen, Bart P.F. Rutten, Daniel L.A. Van Den Hove

Research output: Contribution to journalArticle

Abstract

Brain aging has been associated with aberrant DNA methylation patterns, and changes in the levels of DNA methylation and associated markers have been observed in the brains of Alzheimer's disease (AD) patients. DNA hydroxymethylation, however, has been sparsely investigated in aging and AD. We have previously reported robust decreases in 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in the hippocampus of AD patients compared to non-demented controls. In the present study, we investigated 3- and 9-month-old APPswe/PS1ΔE9 transgenic and wild-type mice for possible age-related alterations in 5-mC and 5-hmC levels in three hippocampal sub-regions using quantitative immunohistochemistry. While age-related increases in levels of both 5-mC and 5-hmC were found in wild-type mice, APPswe/PS1ΔE9 mice showed decreased levels of 5-mC at 9 months of age and no age-related changes in 5-hmC throughout the hippocampus. Altogether, these findings suggest that aberrant amyloid processing impact on the balance between DNA methylation and hydroxymethylation in the hippocampus during aging in mice.

Original languageEnglish (US)
Pages (from-to)190-202
Number of pages13
JournalTranslational Neuroscience
Volume9
Issue number1
DOIs
StatePublished - Dec 31 2018

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Keywords

  • APPswe/PS1ΔE9
  • Aging
  • Alzheimer's Disease
  • DNA hy-droxymethylation
  • DNA methylation
  • Epigenetics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Chouliaras, L., Lardenoije, R., Kenis, G., Mastroeni, DI., Hof, P. R., Os, J. V., Steinbusch, H. W. M., Van Leeuwen, F. W., Rutten, B. P. F., & Van Den Hove, D. L. A. (2018). Age-related disturbances in DNA (hydroxy)methylation in APP/PS1 mice. Translational Neuroscience, 9(1), 190-202. https://doi.org/10.1515/tnsci-2018-0028