The circadian cycle of mPER clock gene products in the suprachiasmatic nucleus of the Siberian hamster encodes both daily and seasonal time

The circadian clock in the hypothalamic suprachiasmatic nuclei (SCN) regulates the pattern of melatonin secretion from the pineal gland such that the duration of release reflects the length of the night. This seasonally specific endocrine cue mediates annual timing in photoperiodic mammals. The aim of this study was to investigate how changes in photoperiod influence the cyclic expression of recently identified clock gene products (mPER and mTIM) in the SCN of a highly seasonal mammal, the Siberian hamster (Phodopus sungorus). Immunocytochemical studies indicate that the abundance of both mPER1 and mPER2 (but not mTIM) in the SCN exhibits very pronounced, synchronous daily cycles, peaking approximately 12 h after lights‐on. These rhythms are circadian in nature as they continue approximately under free‐running conditions. Their circadian waveform is modulated by photoperiod such that the phase of peak mPER expression is prolonged under long photoperiods. mPER1 protein is also expressed in the pars tuberalis of Siberian hamsters. In hamsters adapted to long days, the expression of mPER1 is elevated at the start of the light phase. In contrast, there is no clear elevation in mPER1 levels in the pars tuberalis of hamsters held on short photoperiods. These results indicate that core elements of the circadian clockwork are sensitive to seasonal time, and that encoding and decoding of seasonal information may be mediated by the actions of these transcriptional modulators.

[1]  Steven M Reppert,et al.  mCRY1 and mCRY2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop , 1999, Cell.

[2]  E. Maywood,et al.  Analysis of Clock Proteins in Mouse SCN Demonstrates Phylogenetic Divergence of the Circadian Clockwork and Resetting Mechanisms , 2000, Neuron.

[3]  P. Morgan,et al.  Decoding photoperiodic time through Per1 and ICER gene amplitude. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  N. Mrosovsky,et al.  Rapid down-regulation of mammalian period genes during behavioral resetting of the circadian clock. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A Yasui,et al.  Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. , 1999, Science.

[6]  A. Sehgal,et al.  A role for the proteasome in the light response of the timeless clock protein. , 1999, Science.

[7]  P. Morgan,et al.  The pars tuberalis of the pituitary: a gateway for neuroendocrine output. , 1996, Reviews of reproduction.

[8]  J. Dunlap Molecular Bases for Circadian Clocks , 1999, Cell.

[9]  Yoshiyuki Sakaki,et al.  Circadian oscillation of a mammalian homologue of the Drosophila period gene , 1997, Nature.

[10]  D. P. King,et al.  Role of the CLOCK protein in the mammalian circadian mechanism. , 1998, Science.

[11]  D. Weaver The Suprachiasmatic Nucleus: A 25-Year Retrospective , 1998, Journal of biological rhythms.

[12]  S. Reppert,et al.  A Clockwork Explosion! , 1998, Neuron.

[13]  E. Maywood,et al.  Differential Regulation of mPER1 and mTIM Proteins in the Mouse Suprachiasmatic Nuclei: New Insights into a Core Clock Mechanism , 1999, The Journal of Neuroscience.

[14]  B. Malpaux,et al.  Evidence that melatonin acts in the premammillary hypothalamic area to control reproduction in the ewe: presence of binding sites and stimulation of luteinizing hormone secretion by in situ microimplant delivery. , 1998, Endocrinology.

[15]  D. P. King,et al.  Mammalian Circadian Autoregulatory Loop A Timeless Ortholog and mPer1 Interact and Negatively Regulate CLOCK-BMAL1-Induced Transcription , 1998, Neuron.

[16]  E. Maywood,et al.  Circadian clocks in the mammalian brain. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[17]  Lily Yan,et al.  Light-Induced Resetting of a Mammalian Circadian Clock Is Associated with Rapid Induction of the mPer1 Transcript , 1997, Cell.

[18]  R. R. Margraf,et al.  Melatonin injections affect circadian behavior and SCN neurophysiology in Djungarian hamsters. , 1993, The American journal of physiology.

[19]  H. Eng,et al.  Synthesis of β-Tubulin, Actin, and Other Proteins in Axons of Sympathetic Neurons in Compartmented Cultures , 1999, The Journal of Neuroscience.

[20]  Thomas K. Darlington,et al.  Light-dependent sequestration of TIMELESS by CRYPTOCHROME. , 1999, Science.

[21]  E. Maywood,et al.  Lesions of the melatonin- and androgen-responsive tissue of the dorsomedial nucleus of the hypothalamus block the gonadal response of male Syrian hamsters to programmed infusions of melatonin. , 1996, Biology of reproduction.

[22]  C. Weitz,et al.  Light-independent role of CRY1 and CRY2 in the mammalian circadian clock. , 1999, Science.

[23]  W J Schwartz,et al.  The rat suprachiasmatic nucleus is a clock for all seasons. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Mark J. Zylka,et al.  A Molecular Mechanism Regulating Rhythmic Output from the Suprachiasmatic Circadian Clock , 1999, Cell.

[25]  Joel D Levine,et al.  Molecular Analysis of Mammalian Timeless , 1998, Neuron.

[26]  M. Hastings,et al.  Phosphorylation of CREB in Ovine Pars Tuberalis is Regulated both by cyclic AMP‐Dependent and cyclic AMP‐Independent Mechanisms , 1996, Journal of neuroendocrinology.

[27]  G. Lincoln,et al.  Evidence that Melatonin Acts in the Pituitary Gland through a Dopamine‐independent Mechanism to Mediate Effects of Daylength on the Secretion of Prolactin in the Ram , 1995, Journal of neuroendocrinology.

[28]  D. Hazlerigg,et al.  Photoperiod differentially regulates the expression of Per1 and ICER in the pars tuberalis and the suprachiasmatic nucleus of the Siberian hamster , 2000, The European journal of neuroscience.

[29]  Gregor Eichele,et al.  RIGUI, a Putative Mammalian Ortholog of the Drosophila period Gene , 1997, Cell.

[30]  M. Hastings,et al.  Production of a prolactin releasing factor by the ovine pars tuberalis , 1996, Journal of neuroendocrinology.

[31]  M. Hastings,et al.  Effects of N‐Methyl‐D‐Aspartate (NMDA) on Seasonal Cycles of Reproduction, Body Weight and Pelage Colour in the Male Siberian Hamster , 1995, Journal of neuroendocrinology.

[32]  M. Hastings,et al.  Effect of asymmetrical reductions of photoperiod on pineal melatonin, locomotor activity and gonadal condition of male Syrian hamsters. , 1987, The Journal of endocrinology.

[33]  Markus Meister,et al.  Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms , 1995, Neuron.

[34]  Steven M Reppert,et al.  Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain , 1998, Neuron.

[35]  J. Herbert,et al.  The Suprachiasmatic Nucleus. The Mind's Clock. , 1994 .

[36]  D. Storm,et al.  Light and circadian rhythmicity regulate MAP kinase activation in the suprachiasmatic nuclei , 1998, Nature Neuroscience.

[37]  E. Maywood,et al.  Lesions of the iodomelatonin-binding sites of the mediobasal hypothalamus spare the lactotropic, but block the gonadotropic response of male Syrian hamsters to short photoperiod and to melatonin. , 1995, Endocrinology.

[38]  M. Hastings,et al.  The timed infusion paradigm for melatonin delivery: What has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses? , 1993, Journal of pineal research.

[39]  Josephine Arendt,et al.  Melatonin and the Mammalian Pineal Gland , 1994 .

[40]  P. Morgan,et al.  RAPID COMMUNICATION oPer1 is an Early Response Gene Under Photoperiodic Regulation in the Ovine Pars Tuberalis , 1998, Journal of neuroendocrinology.

[41]  D. Bell-Pedersen,et al.  vvd is required for light adaptation of conidiation-specific genes of Neurospora crassa, but not circadian conidiation. , 2001, Fungal genetics and biology : FG & B.