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 - Funding Information:
Funding: This work was supported by the Internationale Stichting Alzheimer Onderzoek [grant numbers 07551, 11532, 09552]; the Netherlands Organization for Scientific Research [grant numbers 916.11.086, 022.005.019]; the European Commission [grant number MC-EST 020589]; and the National Institutes of Health [grant number P50 AG05138]. The authors declare no conflicts of interest.
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 - Aging
KW - Alzheimer's Disease
KW - APPswe/PS1ΔE9
KW - DNA hy-droxymethylation
KW - DNA methylation
KW - Epigenetics
KW - APPswe/PS1 Delta E9
UR - http://www.scopus.com/inward/record.url?scp=85061113658&partnerID=8YFLogxK
U2 - 10.1515/tnsci-2018-0028
DO - 10.1515/tnsci-2018-0028
M3 - Article
C2 - 30746282
AN - SCOPUS:85061113658
SN - 2081-3856
VL - 9
SP - 190
EP - 202
JO - Translational Neuroscience
JF - Translational Neuroscience
IS - 1
ER -