阿尔茨海默病早期的昼夜节律改变与BMAL1中异常的DNA甲基化循环有关。

Circadian alterations during early stages of Alzheimer's disease are associated with aberrant cycles of DNA methylation in BMAL1.

作者信息

Cronin Peter, McCarthy Michael J, Lim Andrew S P, Salmon David P, Galasko Douglas, Masliah Eliezer, De Jager Philip L, Bennett David A, Desplats Paula

机构信息

Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.

Psychiatry Service, Veterans Affairs San Diego Health Care System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

出版信息

Alzheimers Dement. 2017 Jun;13(6):689-700. doi: 10.1016/j.jalz.2016.10.003. Epub 2016 Nov 22.

DOI:10.1016/j.jalz.2016.10.003

PMID:27883893

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5785929/

Abstract

INTRODUCTION

Circadian alterations are prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, behavioral symptoms, and neurodegeneration. Epigenetic mechanisms regulate the circadian clock, and changes in DNA methylation have been reported in AD brains, but the pathways that mediate circadian deregulation in AD are incompletely understood. We hypothesized that aberrant DNA methylation may affect circadian rhythms in AD.

METHODS

We investigated DNA methylation, transcription, and expression of BMAL1, a positive regulator of the circadian clock, in cultured fibroblasts and brain samples from two independent cohorts of aging and AD.

RESULTS

DNA methylation modulated rhythmic expression of clock genes in cultured fibroblasts. Moreover, rhythmic methylation of BMAL1 was altered in AD brains and fibroblasts and correlated with transcription cycles.

DISCUSSION

Our results indicate that cycles of DNA methylation contribute to the regulation of BMAL1 rhythms in the brain. Hence, aberrant epigenetic patterns may be linked to circadian alterations in AD.

摘要

引言

昼夜节律改变在阿尔茨海默病（AD）中普遍存在，可能导致认知障碍、行为症状和神经退行性变。表观遗传机制调节昼夜节律钟，AD脑内已报道有DNA甲基化变化，但介导AD中昼夜节律失调的途径尚不完全清楚。我们推测异常的DNA甲基化可能影响AD中的昼夜节律。

方法

我们在来自两个独立的衰老和AD队列的培养成纤维细胞和脑样本中，研究了昼夜节律钟的正向调节因子BMAL1的DNA甲基化、转录和表达。

结果

DNA甲基化调节培养成纤维细胞中生物钟基因的节律性表达。此外，AD脑和成纤维细胞中BMAL1的节律性甲基化发生改变，并与转录周期相关。

讨论

我们的结果表明，DNA甲基化循环有助于调节脑中BMAL1的节律。因此，异常的表观遗传模式可能与AD中的昼夜节律改变有关。

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阿尔茨海默病早期的昼夜节律改变与BMAL1中异常的DNA甲基化循环有关。

Circadian alterations during early stages of Alzheimer's disease are associated with aberrant cycles of DNA methylation in BMAL1.

作者信息

Cronin Peter, McCarthy Michael J, Lim Andrew S P, Salmon David P, Galasko Douglas, Masliah Eliezer, De Jager Philip L, Bennett David A, Desplats Paula

机构信息

Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.

Psychiatry Service, Veterans Affairs San Diego Health Care System, San Diego, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.

出版信息

Alzheimers Dement. 2017 Jun;13(6):689-700. doi: 10.1016/j.jalz.2016.10.003. Epub 2016 Nov 22.

DOI:10.1016/j.jalz.2016.10.003

PMID:27883893

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5785929/

Abstract

INTRODUCTION

METHODS

RESULTS

DISCUSSION

Our results indicate that cycles of DNA methylation contribute to the regulation of BMAL1 rhythms in the brain. Hence, aberrant epigenetic patterns may be linked to circadian alterations in AD.

摘要

引言

方法

我们在来自两个独立的衰老和AD队列的培养成纤维细胞和脑样本中，研究了昼夜节律钟的正向调节因子BMAL1的DNA甲基化、转录和表达。

结果

DNA甲基化调节培养成纤维细胞中生物钟基因的节律性表达。此外，AD脑和成纤维细胞中BMAL1的节律性甲基化发生改变，并与转录周期相关。

讨论

我们的结果表明，DNA甲基化循环有助于调节脑中BMAL1的节律。因此，异常的表观遗传模式可能与AD中的昼夜节律改变有关。

阿尔茨海默病早期的昼夜节律改变与BMAL1中异常的DNA甲基化循环有关。

Circadian alterations during early stages of Alzheimer's disease are associated with aberrant cycles of DNA methylation in BMAL1.

作者信息

机构信息

出版信息

INTRODUCTION

METHODS

RESULTS

DISCUSSION

引言

方法

结果

讨论

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阿尔茨海默病早期的昼夜节律改变与BMAL1中异常的DNA甲基化循环有关。

Circadian alterations during early stages of Alzheimer's disease are associated with aberrant cycles of DNA methylation in BMAL1.

作者信息

机构信息

出版信息

INTRODUCTION

METHODS

RESULTS

DISCUSSION

引言

方法

结果

讨论