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Circadian Clock Gene Expression in Brain Regions of Alzheimer ’s Disease Patients and Control Subjects

Cermakian, Nicolas, Waddington Lamont, Elaine, Boudreau, Philippe, Boivin, Diane B.·2011·Journal of Biological Rhythms

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Abstract

Circadian oscillators have been observed throughout the rodent brain. In the human brain, rhythmic expression of clock genes has been reported only in the pineal gland, and little is known about their expression in other regions. The investigators sought to determine whether clock gene expression could be detected and whether it varies as a function of time of day in the bed nucleus of the stria terminalis (BNST) and cingulate cortex, areas known to be involved in decision making and motivated behaviors, as well as in the pineal gland, in the brains of Alzheimer’s disease (AD) patients and aged controls. Relative expression levels of PERIOD1 ( PER1 ), PERIOD2 ( PER2), and Brain and muscle Arnt-like protein-1 (BMAL1) were detected by quantitative PCR in all 3 brain regions. A harmonic regression model revealed significant 24-h rhythms of PER1 in the BNST of AD subjects. A significant rhythm of PER2 was found in the cingulate cortex and BNST of control subjects and in all 3 regions of AD patients. In controls, BMAL1 did not show a diurnal rhythm in the cingulate cortex but significantly varied with time of death in the pineal and BNST and in all 3 regions for AD patients . Notable differences in the phase of clock gene rhythms and phase relationships between genes and regions were observed in the brains of AD compared to those of controls. These results indicate the presence of multiple circadian oscillators in the human brain and suggest altered synchronization among these oscillators in the brain of AD patients.

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Authors: Cermakian, N., Waddington Lamont, E., Boudreau, P., & Boivin, D. B.
Affiliations: Douglas Mental Health University Institute (CA)
Laboratory of Molecular Chronobiology, Douglas Mental Health University Institute, Montréal (QC), Canada, Centre for Study and Treatment of Circadian Rhythms, Douglas Mental Health University Institute, Montréal (QC), Canada, Department of Psychiatry and Department of Neurology and Neurosurgery, McGill University, Montréal (QC), Canada, Department of Neuroscience, Carleton University, Ottawa (ON), Canada.
ORCID: Cermakian, Nicolas
Boudreau, Philippe
Boivin, Diane B.
Venue: Journal of Biological Rhythms
Publisher: SAGE Publications
Published: 2011-03-30
Volume: 26
Issue: 2
Pages: 160-170
ISSN: 0748-7304 (ISSN-L)
1552-4531
DOI: 10.1177/0748730410395732
OpenAlex: W2057817679
Cited by: 175
References: 50
Citations by year: 2026: 4 · 2025: 16 · 2024: 14 · 2023: 12 · 2022: 13 · 2021: 23 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 17 · 2016: 7 · 2015: 10 · 2014: 9 · 2013: 13 · 2012: 3
FWCI: 4.00
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Biological Rhythms (publishedVersion)
PubMed (publishedVersion)
Funders: McGill University
Faculty of Medicine, McGill University
Institut de Recherche Robert-Sauvé en Santé et en Sécurité du Travail
Canadian Institutes of Health Research
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Keywords: clock genes, Alzheimer's disease, circadian clock, bed nucleus of the stria terminalis, cingulate cortex, pineal gland, Per1, Per2, Bmal1, brain aging
MeSH terms: Aged, Alzheimer Disease, Circadian Rhythm, Female, Gyrus Cinguli, Humans, Male, Pineal Gland, Septal Nuclei, Gene Expression, ARNTL Transcription Factors, Period Circadian Proteins, Circadian Clocks

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Circadian Clock Gene Expression in Brain Regions of Alzheimer ’s Disease Patients and Control Subjects

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