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N6-methyladenine is an epigenetic marker of mammalian early life stress.

ABSTRACT: Recent evidence described 6-methyladenine (6?mA) as a novel epigenetic regulator in a variety of multicellular species, including rodents; however, its capacity to influence gene expression in the mammalian brain remains unknown. We examined if 6?mA is present and regulated by early life stress associated with predator odor exposure (POE) within the developing rat amygdala. Our results provide evidence that 6?mA is present in the mammalian brain, is altered within the Htr2a gene promoter by early life stress and biological sex, and increased 6?mA is associated with gene repression. These data suggest that methylation of adenosine within mammalian DNA may be used as an additional epigenetic biomarker for investigating the development of stress-induced neuropathology.

SUBMITTER: Kigar SL

PROVIDER: S-EPMC5741724 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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N<sup>6</sup>-methyladenine is an epigenetic marker of mammalian early life stress.

Kigar Stacey L SL Chang Liza L Guerrero Candace R CR Sehring Jacqueline R JR Cuarenta Amelia A Parker Laurie L LL Bakshi Vaishali P VP Auger Anthony P AP

Scientific reports 20171222 1

Recent evidence described 6-methyladenine (6 mA) as a novel epigenetic regulator in a variety of multicellular species, including rodents; however, its capacity to influence gene expression in the mammalian brain remains unknown. We examined if 6 mA is present and regulated by early life stress associated with predator odor exposure (POE) within the developing rat amygdala. Our results provide evidence that 6 mA is present in the mammalian brain, is altered within the Htr2a gene promoter by earl ...[more]

PMID: 29273787

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Project description:BackgroundIn recent years, the prevalence of Alzheimer's disease (AD) has increased, which places a great burden on society and families and creates considerable challenges for medical services. N6-methyladenine (m6A) deoxyribonucleic acid (DNA) adenine methylation is a novel biomarker and is abundant in the brain, but less common in AD. We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls (NCs) in China.AimTo analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.MethodsA total of 179 AD patients (mean age 71.60 ± 9.89 years; males: 91; females: 88) and 147 NCs (mean age 69.59 ± 11.22 years; males: 77; females: 70) who were age- and sex-matched were included in our study. All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination. Apolipoprotein E (APOE) genotypes were measured through agarose gel electrophoresis. Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit (colorimetric). Global m6A levels in total DNA from ten AD patients with 18F-AV-45 (florbetapir) positron emission tomography (PET) positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.ResultsOur ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs (P = 0.002; < 0.05). And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting. There were significant differences between the two groups, which indicated that the leukocyte m6A DNA levels were different (P = 0.005; < 0.05). The m6A level was approximately 8.33% lower in AD patients than in NCs (mean 0.011 ± 0.006 vs 0.012 ± 0.005). A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population (r = 0.143, P = 0.01; < 0.05). However, no relationship was found with APOE ε4 (P = 0.633, > 0.05). Further studies should be performed to validate these findings.ConclusionOur results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33% in China.

Dataset Information

N6-methyladenine is an epigenetic marker of mammalian early life stress.

Publications

N<sup>6</sup>-methyladenine is an epigenetic marker of mammalian early life stress.

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