DOCSLIB.ORG

Seasonal Molecular Timekeeping Within the Rat Circadian Clock

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Seasonal Molecular Timekeeping Within the Rat Circadian Clock Physiol. Res. 53 (Suppl. 1): S167-S176, 2004 Seasonal Molecular Timekeeping Within the Rat Circadian Clock A. SUMOVÁ, Z. BENDOVÁ, M. SLÁDEK, Z. KOVÁČIKOVÁ, H. ILLNEROVÁ Department of Neurohumoral Regulations, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic Received December 15, 2003 Accepted March 1, 2004 Summary In temperate zones duration of daylight, i.e. photoperiod, changes with the seasons. The changing photoperiod affects animal as well as human physiology. All mammals exhibit circadian rhythms and a circadian clock controlling the rhythms is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of two parts differing morphologically and functionally, namely of the ventrolateral (VL) and the dorsomedial (DM). Many aspects of SCN- driven rhythmicity are affected by the photoperiod. The aim of the present overview is to summarize data about the effect of the photoperiod on the molecular timekeeping mechanism in the rat SCN, especially the effect on core clock genes, clock-controlled genes and clock-related genes expression. The summarized data indicate that the photoperiod affects i) clock-driven rhythm in photoinduction of c-fos gene and its protein product within the VL SCN, ii) clock- driven spontaneous rhythms in clock-controlled, i.e. arginine-vasopressin, and in clock-related, i.e. c-fos, gene expression within the DM SCN, and iii) the core clockwork mechanism within the rat SCN. Hence, the whole central timekeeping mechanism within the rat circadian clock measures not only the daytime but also the time of the year, i.e. the actual season. Key words Suprachiasmatic nucleus • Rat • Photoperiod Introduction The rhythmic production of the pineal hormone melatonin which is a part of the timekeeping system is In temperate zones, daylength, i.e. the also highly photoperiod-dependent, both in nocturnal as photoperiod, changes during the course of the year. The well as in diurnal animals; the high nocturnal melatonin changes in the photoperiod affect mammalian and production is shorter on long summer than on short marginally even human behavior and physiology. winter days (Illnerová and Vaněček 1980, Illnerová 1988, Animals prepare for a forthcoming season by modulating 1991). In humans, a shortening of daylight in the fall their fur, feeding, reproductive, metabolic and locomotor together with a decrease in outdoor light intensity is often activity, etc. In nocturnal rodents, the duration of accompanied by fatigue and seasonal affective disorder locomotor activity reflects the photoperiod as being (Terman et al. 1989). Human physiology may apparently shorter on long summer than on short winter days also adapt to changes in daylength if human subjects (Puchalski and Lynch 1991, Elliot and Tamarkin 1994). experience natural photoperiods; under the long summer PHYSIOLOGICAL RESEARCH ISSN 0862-8408 © 2004 Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic Fax +420 241 062 164 E-mail: [email protected] http://www.biomed.cas.cz/physiolres S168 Sumová et al. Vol. 53 days the melatonin signal may be shorter similarly as is responsible for generation of rhythmicity within the SCN the case with other mammals (Vondrašová et al. 1997, and peripheral rhythmic cells became to be partly Vondrašová-Jelínková et al. 1999). Thus, the photoperiod elucidated by the cloning of mammalian clock genes (Tei may affect significantly the mammalian timekeeping et al. 1997, Shearman et al. 1997, Sun et al. 1997, system. Gekakis et al. 1998, Kume et al. 1999). Eight genes, In mammals, light is perceived solely by the namely three Per (Per1,2,3), two Cry (Cry1, Cry2), retina (Moore 1996). Besides cones and rods mediating Clock, Bmal1 and casein kinase 1 epsilon (CK1ε), are vision, cells in the deep retinal ganglion layer containing thought to be involved in interactive transcriptional- photopigment melanopsin appear to be involved in light translational feedback loops that form the basic molecular perception as well (Provencio et al. 1998, Berson et al. clockwork (for review see King and Takahashi 2000, 2002, Menaker 2003). The ganglion cells may mediate Reppert and Weaver 2001). Briefly, the protein products the “circadian vision”, i.e. inform the circadian system CLOCK and BMAL1 heterodimers positively activate about outdoor lighting conditions in order to keep the rhythmic expression of Per and Cry genes and their endogenous system in proper phase with the outside protein products PER and CRY are produced thereafter. world. The information about light is transduced to the In cytoplasm, the PER and CRY proteins form complexes principal generator of circadian rhythmicity in the important for nuclear translocation of both proteins; the mammalian body located within the suprachiasmatic phosphorylation of PER protein monomers by CK1ε may nuclei (SCN) of the hypothalamus. The connection also regulate their cellular location and stability. After between the retina and the SCN is performed shuttling into the nucleus, the PER:CRY complexes predominantly through a monosynaptic retinohypo- directly interact with the CLOCK:BMAL1 heterodimer thalamic tract or, less extensively, through a polysynaptic and via chromatin remodeling inhibit the geniculohypothalamic tract (Harrington and Rusak 1986). CLOCK:BMAL1 mediated transcription (Etchegaray et In a non-periodic environment, e.g. under al. 2003). Moreover, BMAL1 is negatively autoregulated, constant darkness, the SCN is able to generate and CRY1, CRY2 and PER2 proteins positively activate synchronous oscillations with a period close, but not the Bmal1 transcription (Bae et al. 2001, Zheng et al. equal to 24 h. The actual length of the endogenous period 2001, Yu et al. 2002). The regulation of Bmal1 is genetically given and is species specific. When transcription is likely mediated by REV-ERBα, a protein dissociated in an in vitro culture, most of the SCN cells product of gene Rev-erbα that is controlled by are able to generate independent rhythmic output with CLOCK:BMAL1 (Preitner et al. 2002). Apparently, the different period lengths (Welsh et al. 1995). Moreover, rhythm generating mechanism is very complex and many individual SCN cells differ in their morphological processes which fine-tune the “orchestra” are expected to parameters, peptidergic phenotypes and in function. be revealed in the near future. To convey the rhythmic Whereas cells located predominantly in the ventrolateral signal to periphery, the components of the core clock (VL) part receive photic information from the retina and mechanism serve as transcription factors switching on the express light-dependent rhythmicity, cells located rhythmic transcription of a great array of clock controlled prevalently in the dorsomedial (DM) part do not receive genes within the SCN and peripheral tissues (Jin et al. any direct retinal input and are spontaneously rhythmic 1999, Oishi et al. 2000). (Van den Pol 1991, Sumová et al. 1998, Guido et al. Even less is known about the mechanism 1999a,b, Schwartz et al. 2000). Thus, communication not involved in how light resets the self-oscillating molecular only between individual SCN cells but also between both clockwork. Under light-dark conditions, the circadian parts of the SCN is important for the integration of all clock is entrained by the light period of the day rhythmicity into the resulting output. The output rhythmic (Pittendrigh 1981). Using the clock controlled signal is transduced via humoral and neuronal pathways rhythmicity as a marker, it was shown that a light and controls rhythms in peripheral tissues. Cells of stimulus administered in the evening and early night peripheral tissues are able, to some extent, to produce delays, and a light stimulus administered in the late night local oscillations independent of the SCN (Balsalobre et and early morning advances the rhythmicity (Daan and al. 2000, Yamazaki et al. 2000, Stokkan et al. 2001, Pittendrigh 1976, Illnerová and Vaněček 1982, 1987, McNamara et al. 2001, Terazono et al. 2003). Sumová and Illnerová 1998). Entrainment keeps the The basic molecular core clock mechanism endogenous clock in proper phase with the light-dark 2003 Photoperiod and the Rat Suprachiasmatic Nucleus S169 cycle of the outside world. Information about light is VL part of the rat SCN but not in the DM SCN (Jáč et al. conveyed to retinorecipient SCN cells and mostly 2000b). Importantly, this photic stimulation is phase- glutamate via glutamatergic NMDA and non-NMDA dependent and hence the circadian clock controls the receptors induces different cascades of second light-induced expression of c-fos. The pathway by which messengers in dependence on the time of day (Ebling et the molecular clockwork mediates gating of the photic al. 1991, Ding et al. 1994). Consequently, third response is, however, unclear. During the subjective messengers, namely phosphorylated CREB, are activated. night, the clock-controlled gate is open and light stimuli However, the link connecting the third messenger evoke high c-fos expression in the VL SCN as well as activation and molecular core clock mechanism is still phase shifts of overt rhythms. During the subjective day, not completely understood. Probably, induction of light- the gate is closed and light stimuli evoke neither c-fos sensitive clock genes Per1 and Per2 may proceed through expression nor shifts of the overt rhythms. The time CRE elements of their promotors (Trávníčková-Bendová interval of high photoinduction of c-fos mRNA and cFos- et al. 2002, Tischkau et al. 2003). Even less is known ir may thus serve as a SCN marker of duration of the about the mechanism of how the induced Per1 and Per2 subjective night (Sumová et al. 1995b, Trávníčková et al. mRNAs are involved in resetting the aforementioned 1996, Illnerová et al. 2000). Though it appears that molecular clockwork. Moreover, in mice phase shifts of circadian oscillations in the rat SCN start prenatally output rhythms occur only when light-induced Per1 and (Reppert and Schwartz 1984, Reppert and Uhl 1987, Per2 expression spreads from the VL to the DM parts of Shibata and Moore 1987), the rhythm in cFos the SCN (Yan and Silver 2002).
Load more

Recommended publications
  • Play Clock Operator Guide
    NFHS GENERAL INSTRUCTIONS FOR FOOTBALL GAME AND PLAY CLOCK OPERATORS A. The game and play clock operators should report to the game officials at the stadium at least 30 minutes before game time for the following purposes: 1. To synchronize timer’s watch with official game time as established by the game official responsible for timing. 2. To advise game officials whether the game clock operator and/or play clock operator will be in the press box or on the field/side- line. Determine procedure for communications with both operators and test procedures prior to the games. 3. To discuss coordination of starting, stopping and adjusting the game clock or play clock in accordance with the playing rules. 4. To discuss if the game clock horn (mechanical signal) can be turned off. Preference is for the game clock horn (mechanical signal) to be turned off for the duration of the game. B. The game clock is normally started 30 minutes before game time. The halftime intermission will start on the referee’s signal when the players and game officials leave the field. All pregame and halftime activities shall be synchronized with the game clock. The mandatory three-minute warm-up period will be put on the game clock after the intermission time has elapsed and shall be started immediately. C. The game clock operator shall have an extra stopwatch available. In case of failure of the game clock, the game clock operator shall immediately contact the game officials, giving them the correct data regarding the official time. The game official responsible for timing will then pick up the correct game time on the stopwatch.
    [Show full text]
  • Agonists and Knockdown of Estrogen Receptor Β Differentially Affect
    Schüler-Toprak et al. BMC Cancer (2016) 16:951 DOI 10.1186/s12885-016-2973-y RESEARCH ARTICLE Open Access Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro Susanne Schüler-Toprak1*, Julia Häring1, Elisabeth C. Inwald1, Christoph Moehle2, Olaf Ortmann1 and Oliver Treeck1 Abstract Background: Estrogen receptor β (ERβ) is expressed in the majority of invasive breast cancer cases, irrespective of their subtype, including triple-negative breast cancer (TNBC). Thus, ERβ might be a potential target for therapy of this challenging cancer type. In this in vitro study, we examined the role of ERβ in invasion of two triple-negative breast cancer cell lines. Methods: MDA-MB-231 and HS578T breast cancer cells were treated with the specific ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol. Knockdown of ERβ expression was performed by means of siRNA transfection. Effects on cellular invasion were assessed in vitro by means of a modified Boyden chamber assay. Transcriptome analyses were performed using Affymetrix Human Gene 1.0 ST microarrays. Pathway and gene network analyses were performed by means of Genomatix and Ingenuity Pathway Analysis software. Results: Invasiveness of MBA-MB-231 and HS578T breast cancer cells decreased after treatment with ERβ agonists ERB-041 and WAY200070. Agonists Liquiritigenin and 3β-Adiol only reduced invasion of MDA-MB-231 cells. Knockdown of ERβ expression increased invasiveness of MDA-MB-231 cells about 3-fold. Transcriptome and pathway analyses revealed that ERβ knockdown led to activation of TGFβ signalling and induced expression of a network of genes with functions in extracellular matrix, tumor cell invasion and vitamin D3 metabolism.
    [Show full text]
  • Neurobiological Functions of the Period Circadian Clock 2 Gene, Per2
    Review Biomol Ther 26(4), 358-367 (2018) Neurobiological Functions of the Period Circadian Clock 2 Gene, Per2 Mikyung Kim, June Bryan de la Peña, Jae Hoon Cheong and Hee Jin Kim* Department of Pharmacy, Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul 01795, Republic of Korea Abstract Most organisms have adapted to a circadian rhythm that follows a roughly 24-hour cycle, which is modulated by both internal (clock-related genes) and external (environment) factors. In such organisms, the central nervous system (CNS) is influenced by the circadian rhythm of individual cells. Furthermore, the period circadian clock 2 (Per2) gene is an important component of the circadian clock, which modulates the circadian rhythm. Per2 is mainly expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as other brain areas, including the midbrain and forebrain. This indicates that Per2 may affect various neurobiological activities such as sleeping, depression, and addiction. In this review, we focus on the neurobiological functions of Per2, which could help to better understand its roles in the CNS. Key Words: Circadian rhythm, Per2 gene, Sleep, Depression, Addiction, Neurotransmitter INTRODUCTION and lives in organisms because it can impart effects from the level of cells to organs including the brain. Thus, it is neces- A circadian rhythm is any physiological process that displays sary to understand clock-related genes that are controlling the a roughly 24 hour cycle in living beings, such as mammals, circadian rhythm endogenously. plants, fungi and cyanobacteria (Albrecht, 2012). In organ- The Period2 (Per2) gene is a member of the Period family isms, most biological functions such as sleeping and feeding of genes consisting of Per1, Per2, and Per3, and is mainly patterns are adapted to the circadian rhythm.
    [Show full text]
  • The Period of the Circadian Oscillator Is Primarily Determined by the Balance Between Casein Kinase 1 and Protein Phosphatase 1
    The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1 Hyeong-min Leea,1,2, Rongmin Chena,1, Hyukmin Kima, Jean-Pierre Etchegarayb,3, David R. Weaverb, and Choogon Leea,4 aDepartment of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306; and bDepartment of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605-2324 Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved August 30, 2011 (received for review May 4, 2011) Mounting evidence suggests that PERIOD (PER) proteins play a PAGE—occurs progressively over several hours (12, 19), which is central role in setting the speed (period) and phase of the circadian critical for stretching the feedback loop to ∼24 h. However, PER2 clock. Pharmacological and genetic studies have shown that changes can be maximally phosphorylated by CK1ε in vitro kinase reac- in PER phosphorylation kinetics are associated with changes in tions within 30 min (20, 21), suggesting that PER phosphorylation circadian rhythm period and phase, which can lead to sleep disorders must be counterbalanced by phosphatases in vivo. such as Familial Advanced Sleep Phase Syndrome in humans. We Because the phase and period of the clock are primarily de- and others have shown that casein kinase 1δ and ε (CK1δ/ε) are termined by temporal regulation of PER phosphorylation (12, 15, essential PER kinases, but it is clear that additional, unknown mech- 21–26), the characterization of PER kinases and phosphatases is anisms are also crucial for regulating the kinetics of PER phosphor- vital to understanding the circadian clock mechanism.
    [Show full text]
  • A Mutant Drosophila Homolog of Mammalian Clock Disrupts
    Cell, Vol. 93, 791±804, May 29, 1998, Copyright 1998 by Cell Press AMutantDrosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless Ravi Allada,*²³§ Neal E. White,³ Aronson et al., 1994; Shearman et al., 1997; Sun et al., W. Venus So,²³ Jeffrey C. Hall,²³ 1997; Tei et al., 1997). ²³ and Michael Rosbash* k In Drosophila, there are two well-characterized clock *Howard Hughes Medical Institute genes: period (per) and timeless (tim). Protein levels, ² NSF, Center for Biological Timing RNA levels, and transcription rates of these two genes ³ Department of Biology undergo robust circadian oscillations (Zerr et al., 1990; Brandeis University Hardin et al., 1990, 1992; Hardin, 1994; Sehgal et al., Waltham, Massachusetts 02254 1995; So and Rosbash, 1997). In addition, mutations § Department of Pathology in the two proteins (PER and TIM) alter or abolish the Brigham and Women's Hospital periodicity and phase of these rhythms, demonstrating Boston, Massachusetts 02115 that both proteins regulate their own transcription (Har- din et al., 1990; Sehgal et al., 1995; Marrus et al., 1996). Although there is no evidence indicating that the effects Summary on transcription are direct, PER contains a PAS domain, which has been shown to mediate interactions between We report the identification, characterization, and transcription factors (Huang et al., 1993; Lindebro et cloning of a novel Drosophila circadian rhythm gene, al., 1995). Most of these PAS-containing transcription dClock. The mutant, initially called Jrk, manifests dom- factors also contain the well-characterized basic helix- inant effects: heterozygous flies have a period alter- loop-helix (bHLH) DNA-binding domains (Crews, 1998).
    [Show full text]
  • Circadian Rhythmicity and the Influence of 'Clock
    2311 Z Kiss and P M Ghosh Prostate cancer and the 23:11 T123–T134 Thematic Review ‘clock’ genes WOMEN IN CANCER THEMATIC REVIEW Circadian rhythmicity and the influence of ‘clock’ genes on prostate cancer Zsofia Kiss1,2 and Paramita M Ghosh1,2,3 1VA Northern California Health Care System, Mather, California, USA Correspondence 2Department of Urology, University of California at Davis, Sacramento, California, USA should be addressed 3Department of Biochemistry and Molecular Medicine, University of California at Davis, Sacramento, to P M Ghosh California, USA Email [email protected] Abstract Key Words The androgen receptor (AR) plays a key role in the development and progression f circadian clock of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out f androgen receptor higher incidences of CaP in some select groups, such as airline pilots and night shift f melatonin workers in comparison with those working regular hours. The common finding in these f per1 ‘high-risk’ groups was that they all experienced a deregulation of the body’s internal f bmal1 circadian rhythm. Here, we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression. Circadian rhythmicity of androgen Endocrine-Related Cancer Endocrine-Related production is lost in CaP patients, with the clock genes Per1 and Per2 decreasing, and Bmal1 increasing, in these individuals. Periodic expression of the clock genes was restored upon administration of the neurohormone melatonin, thereby suppressing CaP progression. Activation of the melatonin receptors and the AR antagonized each other, and therefore the tumour-suppressive effects of melatonin and the clock genes were most clearly observed in the absence of androgens, that is, in conjunction with androgen deprivation therapy (ADT).
    [Show full text]
  • BMAL1 and Modulates Tissue-Specific Circadian Networks
    Nuclear receptor HNF4A transrepresses CLOCK: BMAL1 and modulates tissue-specific circadian networks Meng Qua, Tomas Duffyb, Tsuyoshi Hirotac, and Steve A. Kaya,1 aKeck School of Medicine, University of Southern California, Los Angeles, CA 90089; bDepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037; and cInstitute of Transformative Bio-Molecules, Nagoya University, 464-8602 Nagoya, Japan Contributed by Steve A. Kay, November 6, 2018 (sent for review September 24, 2018; reviewed by Carla B. Green and John B. Hogenesch) Either expression level or transcriptional activity of various nuclear NRs canonically function as ligand-activated transcription receptors (NRs) have been demonstrated to be under circadian factors that regulate the expression of their target genes to control. With a few exceptions, little is known about the roles of affect physiological pathways (19). The importance of NRs in NRs as direct regulators of the circadian circuitry. Here we show maintaining optimal physiological homeostasis is illustrated in that the nuclear receptor HNF4A strongly transrepresses the their identification as potential targets for therapeutic drug transcriptional activity of the CLOCK:BMAL1 heterodimer. We development to combat a diverse array of diseases, including define a central role for HNF4A in maintaining cell-autonomous reproductive disorders, inflammation, cancer, diabetes, car- circadian oscillations in a tissue-specific manner in liver and colon diovascular disease, and obesity (20). Various NRs have been cells. Not only transcript level but also genome-wide chromosome implicated as targets of the circadian clock, which may con- binding of HNF4A is rhythmically regulated in the mouse liver. tribute to the circadian regulation of nutrient and energy me- ChIP-seq analyses revealed cooccupancy of HNF4A and CLOCK: tabolism.
    [Show full text]
  • Dissociation of Per1 and Bmal1 Circadian Rhythms in The
    Dissociation of Per1 and Bmal1 circadian rhythms in PNAS PLUS the suprachiasmatic nucleus in parallel with behavioral outputs Daisuke Onoa,1,2, Sato Honmab,1,3, Yoshihiro Nakajimac, Shigeru Kurodad, Ryosuke Enokia,b,e, and Ken-ichi Honmab aPhotonic Bioimaging Section, Research Center for Cooperative Projects, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan; bDepartment of Chronomedicine, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan; cHealth Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Takamatsu, Kagawa 761-0395, Japan; dResearch Institute for Electronic Science, Hokkaido University, Sapporo, 001-0020, Japan; and ePrecursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved March 28, 2017 (received for review August 11, 2016) The temporal order of physiology and behavior in mammals is The expression of Per genes in the SCN is activated by a timed primarily regulated by the circadian pacemaker located in the exposure to light, which phase shifts the circadian pacemaker (8, hypothalamic suprachiasmatic nucleus (SCN). Taking advantage of 9). The phase-dependent phase shifts of clock gene expression bioluminescence reporters, we monitored the circadian rhythms of are regarded as a key mechanism by which the circadian pace- the expression of clock genes Per1 and Bmal1 in the SCN of freely maker is entrained to a LD cycle. Light signals from the retina moving mice and found that the rate of phase shifts induced by a stimulate the expression of Per genes, perturbing the core loop single light pulse was different in the two rhythms.
    [Show full text]
  • Brain Glucocorticoid Receptors Are Necessary for the Rhythmic Expression of The
    * ManuscriptView metadata, citation and similar papers at core.ac.uk brought to you by CORE Click here to view linked References provided by Concordia University Research Repository Brain glucocorticoid receptors are necessary for the rhythmic expression of the clock protein, PERIOD2, in the central extended amygdala in mice 1Segall, L. A., 2Milet, A., 2Tronche, F. and 1Amir, S. 1Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Department of Psychology, Concordia University, Montréal, Québec H4B 1R6, Canada And 2CNRS UMR7148, Molecular Genetics, Neurophysiology and Behavior, Collège de France, 11 place Berthelot, 75231 Paris Cedex 5, France Corresponding Author: Shimon Amir Center for Studies in Behavioral Neurobiology Concordia University, SP-244 7141 Sherbrooke St. West Montreal, QC, Canada H4B 1R6 Tel: 514 848 2424 (EXT 2188) Fax: 514 848 2817 e-mail: [email protected] Acknowledgement Supported by Fonds de la recherche en santé Québec (FRSQ), Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), the Concordia University Research Chairs Program (CRUC), Centre National de la Recherche Scientifique, Agence Nationale de la Recherche (project GRADA) and European Union Framework Program 6 (STREP PheCOMP, NovelTune). Abstract The adrenal glucocorticoid, corticosterone, induces changes in gene expression in both neural and non-neural tissues. The rhythmic release of corticosterone has been shown in rats to be necessary for the rhythmic expression of the clock protein PERIOD2 (PER2) in select regions of the limbic forebrain. The mechanisms mediating the effects of glucocorticoids on changes in gene expression have been linked to the transcriptional activity of the low affinity glucocorticoid receptor, GR.
    [Show full text]
  • Effects of PM Exposure on the Methylation of Clock Genes in a Population of Subjects with Overweight Or Obesity
    International Journal of Environmental Research and Public Health Article Effects of PM Exposure on the Methylation of Clock Genes in A Population of Subjects with Overweight or Obesity Paola Monti 1 , Simona Iodice 2, Letizia Tarantini 2, Francesca Sacchi 2, Luca Ferrari 2 , Massimiliano Ruscica 3 , Massimiliano Buoli 4,5 , Luisella Vigna 1,6 , Angela Cecilia Pesatori 1,2 and Valentina Bollati 2,* 1 Department of Preventive Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; [email protected] (P.M.); [email protected] (L.V.); [email protected] (A.C.P.) 2 EPIGET—Epidemiology, Epigenetics and Toxicology Lab, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy; [email protected] (S.I.); [email protected] (L.T.); [email protected] (F.S.); [email protected] (L.F.) 3 Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy; [email protected] 4 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milan, Italy; [email protected] 5 Department of Neurosciences and Mental Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy 6 Center of Obesity and Work EASO Collaborating Centers for Obesity Management, 20122 Milan, Italy * Correspondence: [email protected]; Tel.: +39-025-032-0127 Abstract: The expression of clock genes, regulating the synchronization of metabolic and behavioral processes with environmental light/dark cycles, is regulated by methylation and might be influenced by short-term exposure to airborne particulate matter (PM), especially in individuals that are hyper- Citation: Monti, P.; Iodice, S.; sensitive to proinflammatory cues.
    [Show full text]
  • The Mammalian Clock Component PERIOD2 Coordinates Circadian Output by Interaction with Nuclear Receptors
    Downloaded from genesdev.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors Isabelle Schmutz,1 Ju¨ rgen A. Ripperger,1 Ste´phanie Baeriswyl-Aebischer, and Urs Albrecht2 Department of Medicine, Unit of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland Mammalian circadian clocks provide a temporal framework to synchronize biological functions. To obtain robust rhythms with a periodicity of about a day, these clocks use molecular oscillators consisting of two interlocked feedback loops. The core loop generates rhythms by transcriptional repression via the Period (PER) and Cryptochrome (CRY) proteins, whereas the stabilizing loop establishes roughly antiphasic rhythms via nuclear receptors. Nuclear receptors also govern many pathways that affect metabolism and physiology. Here we show that the core loop component PER2 can coordinate circadian output with the circadian oscillator. PER2 interacts with nuclear receptors including PPARa and REV-ERBa and serves as a coregulator of nuclear receptor-mediated transcription. Consequently, PER2 is rhythmically bound at the promoters of nuclear receptor target genes in vivo. In this way, the circadian oscillator can modulate the expression of nuclear receptor target genes like Bmal1, Hnf1a, and Glucose-6-phosphatase. The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks. [Keywords: Circadian oscillator; transcription; protein–protein interaction] Supplemental material is available at http://www.genesdev.org. Received October 27, 2009; revised version accepted December 21, 2009. Many changes in physiology and behavior occur rhyth- et al.
    [Show full text]
  • Genetic Markers of Differential Vulnerability to Sleep Loss in Adults
    G C A T T A C G G C A T genes Review Genetic Markers of Differential Vulnerability to Sleep Loss in Adults Courtney E. Casale and Namni Goel * Biological Rhythms Research Laboratory, Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, 1645 W. Jackson Blvd., Suite 425, Chicago, IL 60612, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-312-563-4726 Abstract: In this review, we discuss reports of genotype-dependent interindividual differences in phenotypic neurobehavioral responses to total sleep deprivation or sleep restriction. We highlight the importance of using the candidate gene approach to further elucidate differential resilience and vulnerability to sleep deprivation in humans, although we acknowledge that other omics techniques and genome-wide association studies can also offer insights into biomarkers of such vulnerability. Specifically, we discuss polymorphisms in adenosinergic genes (ADA and ADORA2A), core circadian clock genes (BHLHE41/DEC2 and PER3), genes related to cognitive development and functioning (BDNF and COMT), dopaminergic genes (DRD2 and DAT), and immune and clearance genes (AQP4, DQB1*0602, and TNFa) as potential genetic indicators of differential vulnerability to deficits induced by sleep loss. Additionally, we review the efficacy of several countermeasures for the neurobehavioral impairments induced by sleep loss, including banking sleep, recovery sleep, caffeine, and naps. The discovery of reliable, novel genetic markers of differential vulnerability to sleep loss has critical implications for future research involving predictors, countermeasures, and treatments in the field of sleep and circadian science. Citation: Casale, C.E.; Goel, N. Genetic Markers of Differential Keywords: total sleep deprivation; sleep restriction; candidate genes; polymorphisms; circadian Vulnerability to Sleep Loss in Adults.
    [Show full text]