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Circadian Clock Gene Expression in Brain Regions of Alzheimer ’s Disease Patients and Control Subjects
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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“although individuals with AD still show cycling clock gene expression in multiple brain regions, they lose typical phase coherence within and across regions263”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [263]
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Logan, R. W., & McClung, C. A. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0088-y · Cited by 713
Association between circadian rhythms and neurodegenerative diseases
Leng, Y., Musiek, E. S., Hu, K., Cappuccio, F. P., & Yaffe, K. S. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30461-7 · Cited by 677
Circadian patterns of gene expression in the human brain and disruption in major depressive disorder
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Metadata
- 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.
- 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
- 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
- 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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