| Abstract No.: | B-E2172 |
| Country: | Canada |
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| Title: | CLOCK GENE EXPRESSION IN HUMAN BNST, CINGULATE CORTEX AND PINEAL GLAND OF ALZHEIMER’S DISEASE PATIENTS AND CONTROLS |
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| Authors/Affiliations: | 1 Elaine Waddington Lamont*; 1 Nicolas Cermakian; 1 Diane Boivin;
1 Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada
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| Content: | Objectives: Circadian clock gene expression has been demonstrated in the SCN, cerebellum, cortex, and limbic system of the human brain. Rhythmic clock gene expression has been found in the pineal gland of aged control subjects, but not in that of preclinical or clinical Alzheimer’s Disease (AD) patients. However, an absence of clock gene rhythmicity in the pineal gland has also been reported. We sought to determine whether circadian clock gene expression could be detected in brain regions other than the pineal gland and secondly, whether time of death was a factor in the level of expression of clock gene RNA in human post-mortem brain tissues.
Materials and Methods: Brain tissue from the bed nucleus of the stria terminalis (BNST), cingulate cortex, and pineal gland of AD patients and aged controls were obtained from the Douglas Mental Health University Institute Brain Bank. Total RNA was extracted using a commercially available kit (Qiagen), and verified on agarose gel. Relative expression levels of PERIOD1 (PER1), PERIOD2 (PER2), and BMAL1 were measured in relation to the non-rhythmic housekeeping gene CDK4 using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) with SYBR Green chemistry (Applied Biosystems), and analyzed using the 2-ddCt relative quantification method.
Results: Samples were grouped according to time of death (morning = 06:00-11:59; afternoon = 12:00-17:59; evening = 18:00-23:59; night = 00:00-05:59). Independent two factor analyses of variance (factors: groups x time of day) were performed for each brain region and gene. There was a significant effect of time for PER1 in the cingulate cortex (F[1,3] = 3.09, p<0.05) and pineal gland (F[1,3] = 4.00, p<0.05), with post hoc comparisons revealing that PER1 expression was significantly greater in the evening than at night for both brain regions. There was also a trend for a main effect of time for PER2 in the BNST (F[1,3] = 2.52, p=0.0901), cingulate cortex (F[1,3] = 2.64, p=0.0674) and pineal (F[1,3] = 2.81, p=0.0574).
Conclusion: These results corroborate previous work suggesting a circadian variation of PER1 expression in the human pineal gland and further suggest that there may also be rhythms of PER1 and possibly PER2 expression in the cingulate cortex and BNST, areas known to be involved in decision making and motivated behaviors.
Supported by CIHR and FRSQ.
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