TY - JOUR
T1 - Age-related disturbances in DNA (hydroxy)methylation in APP/PS1 mice
AU - Chouliaras, Leonidas
AU - Lardenoije, Roy
AU - Kenis, Gunter
AU - Mastroeni, DIego
AU - Hof, Patrick R.
AU - Os, Jim Van
AU - Steinbusch, Harry W.M.
AU - Van Leeuwen, Fred W.
AU - Rutten, Bart P.F.
AU - Van Den Hove, Daniel L.A.
N1 - Publisher Copyright:
© 2018 Leonidas Chouliaras et al., published by De Gruyter 2018.
PY - 2018/12/31
Y1 - 2018/12/31
N2 - 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.
AB - 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.
KW - APPswe/PS1ΔE9
KW - Aging
KW - Alzheimer's Disease
KW - DNA hy-droxymethylation
KW - DNA methylation
KW - Epigenetics
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U2 - 10.1515/tnsci-2018-0028
DO - 10.1515/tnsci-2018-0028
M3 - Article
AN - SCOPUS:85061113658
SN - 2081-3856
VL - 9
SP - 190
EP - 202
JO - Translational Neuroscience
JF - Translational Neuroscience
IS - 1
ER -