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

被引:132
作者
Cermakian, Nicolas [1 ,3 ,4 ]
Lamont, Elaine Waddington [1 ,2 ,3 ,4 ]
Boudreau, Philippe [2 ,4 ]
Boivin, Diane B. [2 ,3 ,4 ]
机构
[1] McGill Univ, Douglas Mental Hlth Univ Inst, Lab Mol Chronobiol, Montreal, PQ H4H 1R3, Canada
[2] McGill Univ, Douglas Mental Hlth Univ Inst, Ctr Study & Treatment Circadian Rhythms, Montreal, PQ H4H 1R3, Canada
[3] McGill Univ, Dept Psychiat, Montreal, PQ H4H 1R3, Canada
[4] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H4H 1R3, Canada
基金
加拿大健康研究院;
关键词
circadian clock gene; human; pineal gland; cingulate cortex; bed nucleus of the stria terminalis (BNST); Alzheimer's disease; BLOOD MONONUCLEAR-CELLS; SUPRACHIASMATIC NUCLEUS; PERIPHERAL-TISSUES; SENILE-DEMENTIA; MESSENGER-RNA; RHYTHMS; SLEEP; PATTERNS; BMAL1; MOUSE;
D O I
10.1177/0748730410395732
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:160 / 170
页数:11
相关论文
共 48 条
[1]   Behavioral rhythm splitting in the CS mouse is related to clock gene expression outside the suprachiasmatic nucleus [J].
Abe, H ;
Honma, S ;
Namihira, M ;
Masubuchi, S ;
Honma, K .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2001, 14 (07) :1121-1128
[2]   Independent circadian oscillations of Period1 in specific brain areas in vivo and in vitro [J].
Abraham, U ;
Prior, JL ;
Granados-Fuentes, D ;
Piwnica-Worms, DR ;
Herzog, ED .
JOURNAL OF NEUROSCIENCE, 2005, 25 (38) :8620-8626
[3]   Day-night expression patterns of clock genes in the human pineal gland [J].
Ackermann, Katrin ;
Dehghani, Faramarz ;
Bux, Roman ;
Kauert, Gerold ;
Stehle, Joerg H. .
JOURNAL OF PINEAL RESEARCH, 2007, 43 (02) :185-194
[4]   A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis [J].
Amir, S ;
Lamont, EW ;
Robinson, B ;
Stewart, J .
JOURNAL OF NEUROSCIENCE, 2004, 24 (04) :781-790
[5]  
[Anonymous], 2012, The Jackknife and Bootstrap
[6]   Inter-individual differences in habitual sleep timing and entrained phase of endogenous circadian rhythms of BMAL1, PER2 and PER3 mRNA in human leukocytes [J].
Archer, Simon N. ;
Viola, Antoine U. ;
Kyriakopoulou, Vanessa ;
von Schantz, Malcolm ;
Dijk, Derk-Jan .
SLEEP, 2008, 31 (05) :608-617
[7]   Microarray analysis of postmortem temporal cortex from patients with schizophrenia [J].
Aston, C ;
Jiang, LX ;
Sokolov, BP .
JOURNAL OF NEUROSCIENCE RESEARCH, 2004, 77 (06) :858-866
[8]  
Bauer Martin, 2003, Leg Med (Tokyo), V5, P220, DOI 10.1016/j.legalmed.2003.08.001
[9]   PREDICTORS OF MORTALITY AND INSTITUTIONALIZATION IN ALZHEIMER-DISEASE PATIENTS 1 YEAR AFTER-DISCHARGE FROM AN ALZHEIMER DEMENTIA UNIT [J].
BIANCHETTI, A ;
SCURATTI, A ;
ZANETTI, O ;
BINETTI, G ;
FRISONI, GB ;
MAGNI, E ;
TRABUCCHI, M .
DEMENTIA, 1995, 6 (02) :108-112
[10]   Circadian expression of clock genes in human oral mucosa and skin : Association with specific cell-cycle phases [J].
Bjarnason, GA ;
Jordan, RCK ;
Wood, PA ;
Li, Q ;
Lincoln, DW ;
Sothern, RB ;
Hrushesky, WJM ;
Ben-David, Y .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (05) :1793-1801