The clock gene PER2 and sleep problems: Association with alcohol consumption among Swedish adolescents

Background. Alcohol abuse is associated with sleep problems, which are often linked to circadian rhythm disturbances. Previous studies have separately examined the effects of mutations in the clock gene PER2 on alcohol consumption and sleep problems. Here we hypothesized that an allelic variation in the PER2 gene is associated with alcohol consumption in interaction with sleep problems among adolescents. Methods. The Survey of Adolescent Life and Health in Vastmanland 2006, a Swedish county, including 1254 students 17-18 years old, was used as a population-representative sample of adolescents. We investigated the PER2 Single Nucleotide polymorphism (SNP) 10870 (A/G) in the cohort together with an assessment of alcohol consumption according to the AUDIT-C questionnaire, and sleep problems using a survey consisting of 18 items. Furthermore, we carried out an exploratory analysis on the PER2 Single Nucleotide Polymorphism 10870 polymorphism in a group of severely alcoholic females. Results. We found a significant association of the SNP 10870 in adolescent boys, where the genotype AA, in the presence of several and frequent sleep problems, was associated with increased alcohol consumption. Among adolescent girls, only sleep problems were related to alcohol consumption. A non-significant trend was observed among the severely alcoholic females, with the G allele being over-represented in the severely alcoholic females group in comparision to the control females. Conclusion. These results indicate that PER2 gene variation is associated with alcohol consumption in interaction with sleep problems among Swedish adolescent boys.</p

Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Time‐of‐day‐dependent sensitivity of the reproductive axis to RFamide‐related peptide‐3 inhibition in female Syrian hamsters

In spontaneously ovulating rodent species, the timing of the luteinising hormone (LH) surge is controlled by the master circadian pacemaker in the suprachiasmatic nucleus (SCN). The SCN initiates the LH surge via the coordinated control of two opposing neuropeptidergic systems that lie upstream of the gonadotrophin-releasing hormone (GnRH) neuronal system: the stimulatory peptide, kisspeptin, and the inhibitory peptide, RFamide-related peptide-3 (RFRP-3; the mammalian orthologue of avian gonadotrophin-inhibitory hormone [GnIH]). We have previously shown that the GnRH system exhibits time-dependent sensitivity to kisspeptin stimulation, further contributing to the precise timing of the LH surge. To examine whether this time-dependent sensitivity of the GnRH system is unique to kisspeptin or a more common mechanism of regulatory control, we explored daily changes in the response of the GnRH system to RFRP-3 inhibition. Female Syrian hamsters were ovariectomised to eliminate oestradiol (E2 )-negative-feedback and RFRP-3 or saline was centrally administered in the morning or late afternoon. LH concentrations and Lhβ mRNA expression did not differ between morning RFRP-3-and saline-treated groups, although they were markedly suppressed by RFRP-3 administration in the afternoon. However, RFRP-3 inhibition of circulating LH at the time of the surge does not appear to act via the GnRH system because no differences in medial preoptic area Gnrh or RFRP-3 receptor Gpr147 mRNA expression were observed. Rather, RFRP-3 suppressed arcuate nucleus Kiss1 mRNA expression and potentially impacted pituitary gonadotrophs directly. Taken together, these findings reveal time-dependent responsiveness of the reproductive axis to RFRP-3 inhibition, possibly via variation in the sensitivity of arcuate nucleus kisspeptin neurones to this neuropeptide