Alternation between short- and long photoperiod reveals hypothalamic gene regulation linked to seasonal body weight changes in Djungarian hamsters (Phodopus sungorus)

This work was funded by the German Research Foundation (DFG, Emmy-Noether HE6383 to AH) and the British Society for Neuroendocrinology (Research grant to JB). The authors declare that they have no conflicts of interest.Peer reviewedPostprin

Seasonal Control of Mammalian Energy Balance : Recent advances in the understanding of daily torpor and hibernation

Funding This work was supported in part by BBSRC grant (BB/M001504/1) to PB, DFG Emmy-Noether HE6383 to AH, German Center for Diabetes Research (DZD) to MJ.Peer reviewedPostprin

Seasonal Control of Mammalian Energy Balance : Recent advances in the understanding of daily torpor and hibernation

Funding This work was supported in part by BBSRC grant (BB/M001504/1) to PB, DFG Emmy-Noether HE6383 to AH, German Center for Diabetes Research (DZD) to MJ.Peer reviewedPostprin

Orchestration of gene expression across the seasons : Hypothalamic gene expression in natural photoperiod throughout the year in the Siberian hamster

Acknowledgements Funding for work in the laboratory of PB was supported by Scottish Government Rural and Environment Science and Analytical Services Division, BBSRC (grant BB/M001504/1), British Society for Neuroendocrinology (research visit grant to IP). Work in the laboratory of SS was supported by a grant from the DFG (Ste 331/8-1). We thank Siegried Hilken, Marianne Brüning, Dr. Esther Lipokatic-Takacs and Dr. Frank Scherbarth at UVMH for technical assistance. We thank Graham Horgan of Bioinformatics, Statistics Scotland for assistance with some of statistical tests.Peer reviewedPublisher PD

Hypothalamic ventricular ependymal thyroid hormone deiodinases are an important element of circannual timing in the siberian hamster (Phodopus sungorus)

Exposure to short days (SD) induces profound changes in the physiology and behaviour of Siberian hamsters, including gonadal regression and up to 30% loss in body weight. In a continuous SD environment after approximately 20 weeks, Siberian hamsters spontaneously revert to a long day (LD) phenotype, a phenomenon referred to as the photorefractory response. Previously we have identified a number of genes that are regulated by short photoperiod in the neuropil and ventricular ependymal (VE) cells of the hypothalamus, although their importance and contribution to photoperiod induced physiology is unclear. In this refractory model we hypothesised that the return to LD physiology involves reversal of SD expression levels of key hypothalamic genes to their LD values and thereby implicate genes required for LD physiology. Male Siberian hamsters were kept in either LD or SD for up to 39 weeks during which time SD hamster body weight decreased before increasing, after more than 20 weeks, back to LD values. Brain tissue was collected between 14 and 39 weeks for in situ hybridization to determine hypothalamic gene expression. In VE cells lining the third ventricle, expression of nestin, vimentin, Crbp1 and Gpr50 were down-regulated at 18 weeks in SD photoperiod, but expression was not restored to the LD level in photorefractory hamsters. Dio2, Mct8 and Tsh-r expression were altered by SD photoperiod and were fully restored, or even exceeded values found in LD hamsters in the refractory state. In hypothalamic nuclei, expression of Srif and Mc3r mRNAs was altered at 18 weeks in SD, but were similar to LD expression values in photorefractory hamsters. We conclude that in refractory hamsters not all VE cell functions are required to establish LD physiology. However, thyroid hormone signalling from ependymal cells and reversal of neuronal gene expression appear to be essential for the SD refractory response

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.</p> <p>Methods</p> <p>For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.</p> <p>Results</p> <p>The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.</p> <p>Conclusions</p> <p>The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.</p

Torpor und Timing, der Einfluss endogen kontrollierter Hypothermie auf das circadiane System zweier Hamsterspezies

L'influence des saisons est extrêmement marquée au niveau des hautes latitudes du globe, avec des variations des conditions environnementales très prononcées. Les Mammifères vivant dans de telles conditions drastiques, ont développés différentes formes d'hibernation (ou torpeur) pour réduire les coûts métaboliques pendant ces périodes rudes lorsque les ressources énergétiques se font rares. Les Mammifères hibernants comme le Hamster d'Europe (Cricetus cricetus), dont la température corporelle (Tb) diminue pendant plusieurs jours pour atteindre des niveaux voisins de la température ambiante (Ta), peuvent ainsi préserver au maximum leurs réserves d'énergie. Au contraire, quelques petits Mammifères comme le Hamster de Djungarie (Phodopus sungorus) montrent des hypothermies journalières de moindre amplitude. Ils utilisent les quelques heures de leur temps de repos circadien pour effectuer avec précision des hypothermies contrôlées, et diminuer leur Tb jusqu à un seuil minimal de 15 °C. De telles Tb basses qui se prolongent, peuvent avoir des conséquences sur l'activité du système nerveux central (SNC). Il est donc crucial que l'intégralité fonctionnelle du SNC soit maintenue, ainsi, la limitation de la durée d'hypothermie permet un réveil régulier à des Tas basses. Pendant la torpeur, un des systèmes régulateurs importants serait le système circadien, car il réagit à la photopériode et synchronise les phénomènes internes sur une base de temps circadienne. Dans ce travail de thèse, nous avons pu montrer, pour la première fois, que la machinerie moléculaire de l'horloge biologique endogène reste active pendant la torpeur chez le Hamster de Djungarie mais une chute de la Tb diminue l'amplitude de l'expression des gènes de l'horloge biologique circadienne. La diminution de l'expression des protéines pendant l'hypothermie, induirait une diminution du rétrocontrôle de la transcription pendant et après une période de torpeur. Pour mieux comprendre les changements d'expression de ces gènes, nous avons déterminé par microdialyse trans-pineal les sécrétions de mélatonine (hormone reflétant l'activité de la principale sortie de l'horloge ), pendant une longue durée. Cette méthode, qui a été adaptée pour la première fois au Hamster de Djungarie (animal de petite taille), s'avère être un bon outil pour étudier les signaux saisonniers comme la mélatonine chez les animaux hibernants. Pendant l'hibernation du Hamster d'Europe, la diminution de la Tb atteint ~8 °C pendant quelques jours dans nos conditions expérimentales. A basse température, nous n avons pas pu observer de rythme de l'expression des gènes de l'horloge biologique ce qui indiquerait dans ces conditions un arrêt des oscillations. A partir de nos résultats, nous avons conclu que l'horloge circadienne semble compenser les effets d'une diminution de la Tb dans un large gradient mais au delà d'un certain seuil de température les oscillations sont arrêtées.Seasonal influences become increasingly important at high latitudes, where variations in external conditions are most pronounced. Mammals living in such drastic conditions have developed different forms of torpor to reduce metabolic costs in harsh periods when energy is rare. Deep hibernators like the European hamster (Cricetus cricetus) regularly decrease their body temperature (Tb) for several days to temperatures approaching ambient temperature (Ta) and thereby save a maximum of energy. In contrast some small mammals like the Djungarian hamster (Phodopus sungorus) undergo shallower bouts of daily torpor. Induced by short photoperiod they spontaneously use their daily resting time for only a few hours of precisely timed hypothermia during which their body temperature decreases to minimum 15°C. Invariably low Tbs go along with a depression of CNS activity. Nevertheless it is crucial that functional integrity is maintained, which is why systems of vital importance during hypothermia are supposed to remain active at those low Tbs. One of the important keys during torpor is believed to be the circadian system. It measures photoperiod and thereby determines the onset of the torpor season and moreover synchronizes internal processes on a circadian basis. In this thesis we could for the first time demonstrate that the clock s molecular machinery is still active during daily torpor in Djungarian hamsters. Alterations in phase and amplitude of clock gene expression rhythms however, point to temperature sensitivity. Decrease in protein expression during hypothermia, hence a decreased feedback might be responsible for transcriptional alterations during and after a torpor bout. To more precisely investigate phase changes seen in gene expression, we set up a long term microdialysis experiment to continuously measure melatonin, a well defined clock output, in vivo directly in the pineal gland. This method could for the first time be adapted to the very small Djungarian hamster and provides a good tool to study a circadian signal like melatonin in a seasonally heterothermic animal. During deep hibernation in European hamsters that decreased their Tb for several days to ~8°C in our experimental conditions, we could not observe any rhythmic clock gene expression and thereby show that the clock stops oscillating at those low temperatures. We conclude from our data, that the circadian clock seems to be temperature compensated in a wide temperature range but once a certain low temperature is reached, oscillation is no longer possible.Einflüsse saisonaler Umweltveränderungen (z.B Photoperiode und Umgebungstemperatur) verstärken sich mit zunehmender geographischer Breite, und Säugetiere, die unter solch extrem variablen Bedingungen leben, haben unterschiedliche Formen von Torpor entwic

Torpor und Timing, der Einfluss endogen kontrollierter Hypothermie auf das circadiane System zweier Hamsterspezies

L'influence des saisons est extrêmement marquée au niveau des hautes latitudes du globe, avec des variations des conditions environnementales très prononcées. Les Mammifères vivant dans de telles conditions drastiques, ont développés différentes formes d'Seasonal influences become increasingly important at high latitudes, where variations in external conditions are most pronounced. Mammals living in such drastic conditions have developed different forms of torpor to reduce metabolic costs in harsh periodsEinflüsse saisonaler Umweltveränderungen (z.B Photoperiode und Umgebungstemperatur) verstärken sich mit zunehmender geographischer Breite, und Säugetiere, die unter solch extrem variablen Bedingungen leben, haben unterschiedliche Formen von Torpor entwic

Hypothalamic control systems show differential gene expression during spontaneous daily torpor and fasting-induced torpor in the Djungarian hamster (Phodopus sungorus).

Djungarian hamsters are able to use spontaneous daily torpor (SDT) during the winter season as well as fasting-induced torpor (FIT) at any time of the year to cope with energetically challenging environmental conditions. Torpor is a state of severely reduced metabolism with a pronounced decrease in body temperature, which enables animals to decrease their individual energy requirements. Despite sharing common characteristics, such as reduced body mass before first torpor expression and depressed metabolism and body temperature during the torpid state, FIT and SDT differ in several physiological properties including torpor bout duration, minimal body temperature, fuel utilization and circadian organization. It remains unclear, whether SDT and FIT reflect the same phenomenon or two different physiological states. The hypothalamus has been suggested to play a key role in regulating energy balance and torpor. To uncover differences in molecular control mechanisms of torpor expression, we set out to investigate hypothalamic gene expression profiles of genes related to orexigenic (Agrp/Npy), circadian clock (Bmal1/Per1) and thyroid hormone (Dio2/Mct8) systems of animals undergoing SDT and FIT during different torpor stages. Orexigenic genes were mainly regulated during FIT and remained largely unaffected by SDT. Expression patterns of clock genes showed disturbed circadian clock rhythmicity in animals undergoing FIT, but not in animals undergoing SDT. During both, SDT and FIT, decreased Dio2 expression was detected, indicating reduced hypothalamic T3 availability in both types of torpor. Taken together, our results provide evidence that SDT and FIT also differ in certain central control mechanisms and support the observation that animals undergoing SDT are in energetical balance, whereas animals undergoing FIT display a negative energy balance. This should be carefully taken into account when interpreting data in torpor research, especially from animal models of fasting-induced hypometabolism such as mice