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/PS1 Delta E9 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/PS1 Delta E9 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 language | English |
|---|---|
| Pages (from-to) | 190-202 |
| Number of pages | 13 |
| Journal | Translational Neuroscience |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jan 2018 |
Keywords
- Aging
- Alzheimer's Disease
- APPswe/PS1 Delta E9
- Epigenetics
- DNA methylation
- DNA hy-droxymethylation
- APPSWE/PS1DE9 MOUSE MODEL
- ALZHEIMERS-DISEASE
- AMYLOID DEPOSITION
- EPIGENETIC MODIFICATIONS
- PLAQUE-FORMATION
- MEMORY DEFICITS
- GENE-EXPRESSION
- TRANSGENIC MICE
- GLOBAL DNA
- LEAD PB