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

被引：101

作者：

Cronin, Peter ^{[1
]}

McCarthy, Michael J. ^{[2
,3
]}

Lim, Andrew S. P. ^{[4
]}

Salmon, David P. ^{[1
]}

Galasko, Douglas ^{[1
]}

Masliah, Eliezer ^{[1
,5
]}

De Jager, Philip L. ^{[6
,7
]}

Bennett, David A. ^{[8
]}

Desplats, Paula ^{[1
,5
]}

机构：

[1] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[2] Vet Affairs San Diego Hlth Care Syst, Psychiat Serv, San Diego, CA USA

[3] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[4] Univ Toronto, Div Neurol, Dept Med, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada

[5] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[6] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA

[7] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA

[8] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA

来源：

ALZHEIMERS & DEMENTIA | 2017年 / 13卷 / 06期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

DNA methylation; Circadian rhythms; Methylation cycles; Alzheimer's disease; BMAL1; Neurodegeneration; Epigenetics; Fibroblasts; Circadian clock; Brain; CLOCK GENE-EXPRESSION; RHYTHMS; SLEEP; DISRUPTION; BRAIN; DEMENTIA; PATTERNS;

D O I：

10.1016/j.jalz.2016.10.003

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

引用

页码：689 / 700

页数：12

共 48 条

[1] SIRT1 regulates circadian clock gene expression through PER2 deacetylation [J].

Asher, Gad ;

Gatfield, David ;

Stratmann, Markus ;

Reinke, Hans ;

Dibner, Charna ;

Kreppel, Florian ;

Mostoslavsky, Raul ;

Alt, Frederick W. ;

Schibler, Ueli .

CELL, 2008, 134 (02) :317-328

[2] Circadian behavior is light-reprogrammed by plastic DNA methylation [J].

Azzi, Abdelhalim ;

Dallmann, Robert ;

Casserly, Alison ;

Rehrauer, Hubert ;

Patrignani, Andrea ;

Maier, Bert ;

Kramer, Achim ;

Brown, Steven A. .

NATURE NEUROSCIENCE, 2014, 17 (03) :377-382

[3] CHD1 Remodels Chromatin and Influences Transient DNA Methylation at the Clock Gene frequency [J].

Belden, William J. ;

Lewis, Zachary A. ;

Selker, Eric U. ;

Loros, Jennifer J. ;

Dunlap, Jay C. .

PLOS GENETICS, 2011, 7 (07)

[4]

Bennett DA, 2012, CURR ALZHEIMER RES, V9, P646

[5]

Bennett DA, 2012, CURR ALZHEIMER RES, V9, P628

[6] Molecular insights into human daily behavior [J].

Brown, Steven A. ;

Kunz, Dieter ;

Dumas, Amelie ;

Westermark, Pal O. ;

Vanselow, Katja ;

Tilmann-Wahnschaffe, Amely ;

Herzel, Hanspeter ;

Kramer, Achim .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (05) :1602-1607

[7]

Buhr Ethan D, 2013, Handb Exp Pharmacol, P3, DOI 10.1007/978-3-642-25950-0_1

[8] Perinatal photoperiod imprints the circadian clock [J].

Ciarleglio, Christopher M. ;

Axley, John C. ;

Strauss, Benjamin R. ;

Gamble, Karen L. ;

McMahon, Douglas G. .

NATURE NEUROSCIENCE, 2011, 14 (01) :25-27

[9] Disrupted Daytime Activity and Altered Sleep-Wake Patterns May Predict Transition to Mild Cognitive Impairment or Dementia A Critically Appraised Topic [J].

Covell, Gretchen E. Schlosser ;

Dhawan, Priya S. ;

Iannotti, Joyce K. Lee ;

Hoffman-Snyder, Charlene R. ;

Wellik, Kay E. ;

Caselli, Richard J. ;

Woodruff, Bryan K. ;

Wingerchuk, Dean M. ;

Demaerschalk, Bart M. .

NEUROLOGIST, 2012, 18 (06) :426-429

[10] Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci [J].

De Jager, Philip L. ;

Srivastava, Gyan ;

Lunnon, Katie ;

Burgess, Jeremy ;

Schalkwyk, Leonard C. ;

Yu, Lei ;

Eaton, Matthew L. ;

Keenan, Brendan T. ;

Ernst, Jason ;

McCabe, Cristin ;

Tang, Anna ;

Raj, Towfique ;

Replogle, Joseph ;

Brodeur, Wendy ;

Gabriel, Stacey ;

Chai, High S. ;

Younkin, Curtis ;

Younkin, Steven G. ;

Zou, Fanggeng ;

Szyf, Moshe ;

Epstein, Charles B. ;

Schneider, Julie A. ;

Bernstein, Bradley E. ;

Meissner, Alex ;

Ertekin-Taner, Nilufer ;

Chibnik, Lori B. ;

Kellis, Manolis ;

Mill, Jonathan ;

Bennett, David A. .

NATURE NEUROSCIENCE, 2014, 17 (09) :1156-1163

← 1 2 3 4 5 →