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APP/PS1小鼠中与年龄相关的DNA（羟基）甲基化紊乱

Age-related Disturbances in DNA (hydroxy)methylation in APP/PS1 Mice.

作者信息

Chouliaras Leonidas, Lardenoije Roy, Kenis Gunter, Mastroeni Diego, Hof Patrick R, van Os Jim, Steinbusch Harry W M, van Leeuwen Fred W, Rutten Bart P F, van den Hove Daniel L A

机构信息

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, The Netherlands.

Current: Department of Psychiatry, University of Cambridge, Cambridge UK.

出版信息

Transl Neurosci. 2018 Dec 31;9:190-202. doi: 10.1515/tnsci-2018-0028. eCollection 2018.

DOI:10.1515/tnsci-2018-0028
PMID:30746282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6368665/
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.

摘要

脑老化与异常的DNA甲基化模式有关，并且在阿尔茨海默病（AD）患者的大脑中已观察到DNA甲基化水平及相关标志物的变化。然而，DNA羟甲基化在衰老和AD中的研究较少。我们之前报道过，与非痴呆对照相比，AD患者海马体中的5-甲基胞嘧啶（5-mC）和5-羟甲基胞嘧啶（5-hmC）显著减少。在本研究中，我们使用定量免疫组化方法，研究了3个月和9个月大的APPswe/PS1ΔE9转基因小鼠和野生型小鼠三个海马亚区中5-mC和5-hmC水平可能存在的与年龄相关的变化。虽然在野生型小鼠中发现5-mC和5-hmC水平均有与年龄相关的增加，但APPswe/PS1ΔE9小鼠在9个月大时5-mC水平降低，且整个海马体中5-hmC没有与年龄相关的变化。总之，这些发现表明，异常的淀粉样蛋白加工会影响小鼠衰老过程中海马体中DNA甲基化和羟甲基化之间的平衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/f9133b53fdba/tnsci-09-190-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/4fbb23679859/tnsci-09-190-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/800a1d6492a4/tnsci-09-190-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/08801e65d455/tnsci-09-190-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/94a1e6fecec4/tnsci-09-190-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/1daff834dd9b/tnsci-09-190-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/94bfcac664d6/tnsci-09-190-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/f9133b53fdba/tnsci-09-190-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/4fbb23679859/tnsci-09-190-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/800a1d6492a4/tnsci-09-190-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/08801e65d455/tnsci-09-190-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/94a1e6fecec4/tnsci-09-190-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/1daff834dd9b/tnsci-09-190-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/94bfcac664d6/tnsci-09-190-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57ae/6368665/f9133b53fdba/tnsci-09-190-g007.jpg

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