Journal
NEUROSCIENCE
Volume 171, Issue 2, Pages 398-406Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2010.09.009
Keywords
Aanat; circadian amplitude modulation; negative regulator complex
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Funding
- Deutsche Forschungsgememschaft
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Melatonin is an important endocrine signal for darkness in mammals Transcriptional activation of the arylalkylamine N-acetyltransferase gene encoding for the penultimate enzyme in melatonin synthesis drives the daily rhythm of the hormone in the pineal gland of rodents Rhythmic arylalkylanune-N acetyltransferase expression is controlled by the cAMP signal transduction pathway and involves the activation of beta adrenergic receptors and the inducible cAMP early repressor In addition, the rat arylalkylamine N-acetyltransferase promoter contains an E box element which can interact with clock proteins Moreover the pineal gland of mice shows a circadian rhythm in clock proteins such as the transcriptional repressor Period1, which has been shown to control rhythmic gene expression in a variety of tissues However the role of Period1 in the regulation of pineal melatonin synthesis is still unknown Therefore, circadian rhythms in arylalkylamine N acetyltransferase, beta adrenergic receptor and inducible cAMP early repressor mRNA levels (real time PCR) arylalkylamine N acetyltransferase enzyme activity (radiometric assay) and melatonin concentration radio immuno assay (RIA) were analyzed in the pineal gland of mice with a targeted deletion of the Period1 gene (Per1-/-) and the corresponding wildtype In Per1-/- the amplitude in arylalkylamine N-acetyltransferase expression was significantly elevated as compared to wildtype In contrast, beta adrenergic receptor and inducible cAMP early repressor mRNA levels were not affected by the Period1 deficiency This indicates that the molecular clockwork alters the amplitude of arylalkylamine N-acetyltransferase expression In vitro, pineal glands of Per1-/- mice showed a day night difference in arylalkylamine N-acetyltransferase expression with high levels at night This suggests that a deficient in Period1 elicits similar effects as the activation of the cAMP signal transduction pathway in wildtype mice (C) 2010 IBRO Published by Elsevier Ltd All rights reserved
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