Reduced Expression of Circadian Clock Genes in Male Alcoholic Patients

Huang, Ming; Ho, Chia Wei; Chen, Chun Hsin; Liu, Shing Cheng; Chen, Chiao Chicy; Leu, Sy Jye

doi:10.1111/j.1530-0277.2010.01278.x

Cited by 75 publications

(50 citation statements)

References 33 publications

(58 reference statements)

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“…However, the additive effect of LL-induced chronodisruption on ethanol intake in ENT1 KO mice validates the idea that pre-existing circadian misalignment may increase ethanol consumption during environmental challenges to the circadian system. Our findings implicate ENT1 and adenosine receptormediated signaling in alcohol-induced flattening of Per gene rhythms (Chen et al, 2004;Huang et al, 2010). Specifically, A1R inhibition downregulated Per1 and Per2 expression, whereas A2AR inhibition downregulated only Per2.…”

Section: Discussionmentioning

confidence: 72%

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Ruby

Vadnie

Hinton

et al. 2014

Neuropsychopharmacol

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Circadian rhythm and sleep disruptions occur frequently in individuals with alcohol use disorders (AUD) and present significant barriers to treatment. Recently, a variant of adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), was associated with the cooccurrence of sleep problems and AUD. We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum and drink more alcohol compared with wild types (WT). However, it is unknown whether ENT1 deletion disrupts circadian rhythms, which may contribute to alcohol preference in ENT1 KO mice. Here we used these mice to determine whether endogenous adenosine regulates circadian genetic and behavioral rhythms and influences alcohol intake during chronodisruption. We examined circadian locomotor activity in ENT1 KO vs WT littermates and found that ENT1 KO mice were both active earlier and hyperactive compared with WT mice at night. We used real-time PCR and immunohistochemistry to estimate striatal clock gene levels and found that PER2 expression in the striatum was blunted by ENT1 deletion or A2A receptor (A2AR) antagonism. Next, we exposed ENT1 KO and WT mice to constant light (LL) and found further elevation in ethanol intake in ENT1 KO, but not in WT mice, supporting the notion that circadian dysfunction may contribute to increased alcohol intake in ENT1 KO mice. Finally, we showed that A2AR agonist administration normalized PER1 and PER2 expression and circadian locomotor activity in ENT1 KO mice. Together, our results demonstrate that adenosine signaling regulates cellular and behavioral circadian timing and influences alcohol intake during chronodisruption.

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Section: Discussionmentioning

confidence: 72%

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

Ruby

Vadnie

Hinton

et al. 2014

Neuropsychopharmacol

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“…The lack of regularity in circadian rhythms has been mostly studied with alcohol (Conroy et al, 2012;Danel & Touitou, 2004;Huang et al, 2010;Rupp et al, 2007), tobacco (Adan & Sanchez-Turet, 1995Adan et al, 2004), and cocaine dependence (McClung et al, 2005;Uz et al, 2005). However, it seems that the data compiled to date may be generalized to most types of drugs, independently of their pharmacological effects on the organism (Perreau-Lenz & Spanagel, 2008;Adan, 2012).…”

Section: Addictionsmentioning

confidence: 99%

“…There is also evidence that circadian genes play a role in addiction. The circadian gene Clock is a direct regulator of the dopaminergic activity in the brain areas of reward (Huang et al, 2010;Rosenwasser, 2010), Per1 has been related to rewarding properties (McClung, 2007), and Per2 has been proven essential to inhibit the sensitization and reward to the effects of drugs (PerreauLenz & Spanagel, 2008;Perreau-Lenz et al, 2009).…”

Section: Addictionsmentioning

confidence: 99%

Circadian Typology: A Comprehensive Review

Adán¹,

Archer²,

Hidalgo³

et al. 2012

Chronobiology International

1,033

855

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The interest in the systematic study of the circadian typology (CT) is relatively recent and has developed rapidly in the two last decades. All the existing data suggest that this individual difference affects our biological and psychological functioning, not only in health, but also in disease. In the present study, we review the current literature concerning the psychometric properties and validity of CT measures as well as individual, environmental and genetic factors that influence the CT. We present a brief overview of the biological markers that are used to define differences between CT groups (sleep-wake cycle, body temperature, cortisol, and melatonin), and we assess the implications for CT and adjustment to shift work and jet-lag. We also review the differences between CT in terms of cognitive abilities, personality traits and the incidence of psychiatric disorders. When necessary, we have emphasized the methodological limitations that exist today and suggested some future avenues of work in order to overcome these. This is a new field of interest to professionals in many different areas (research, labor, academic, and clinical) and this review provides a state of the art discussion to allow professionals to integrate chronobiological aspects of human behavior into their daily practice.

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“…Therefore, they may have important relevance to the carcinogenic process. Alteration of circadian genes was found to be associated with various disorders in humans, including sleep and mental disorders, cardiovascular diseases, obesity, impaired glucose tolerance, alcohol abuse, and cancer (8)(9)(10)(11)(12).…”

mentioning

confidence: 99%