Dr Raphaelle Winsky-Sommerer

Senior Lecturer in Sleep & Circadian Rhythms

Qualifications: BSc, MSc, PhD, Dr. Habil.

Email:
Phone: Work: 01483 68 9671

Further information

Biography

Senior Lecturer in Sleep & Circadian Rhythms (since April 2012)
Faculty of Health and Medical Sciences, University of Surrey, UK.

Lecturer in Sleep & Circadian Rhythms (October 2009)
Faculty of Health and Medical Sciences, University of Surrey, UK.

Research Associate in Sleep & Chronobiology (2004-2009)
Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.

Post-doctoral Research Fellow in Neuroscience (2002-2004)
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.

Ph.D. Cellular & Molecular Biology, Biology of Ageing (1998-2002)
University of René Descartes Paris 5, France. INSERM U549, Paris, France.

Master in Biochemistry & Biology of Ageing (1996-1998)
(Master I in Biochemistry; Master II = French DEA in Biology of Ageing)
University of Paris 5 & 7, France.

Bachelor of Science in Biochemistry (1994-1996)
University of Paris 7, France.  

Research Interests

Sleep & Circadian Rhythms – Pharmacology of Sleep and Wakefulness
Cellular and molecular mechanisms underlying the regulation of the daily sleep-wake cycle; Hypnotics and wake-promoting compounds.

Physiology of Neurotransmitter & Neuropeptide Systems
GABAergic transmission and GABAA receptors; adenosinergic system; neuropeptides (i.e., hypocretins/orexins, corticotrophin-releasing hormone, somatostatin/cortistatin, vasopressin, oxytocin).

Disorders of the Central Nervous System - Aging
Insomnia; Stress; Addiction; Aging; Neurodegenerative diseases (i.e., Alzheimer’s disease)

 

Funding received

  • New Investigator Research Grant- British Biotechnology and Biological Sciences Research Council; BB/I008926/1; 2011-2014; £494,741; 36 months; to R. Winsky-Sommerer (PI).
  • Investigator-initiated Research Grant- Pharmaceutical Company; £157,745; 12 months; to R. Winsky-Sommerer (PI), D-J Dijk, S. Archer.
  • Feasibility Study Grant- MILES (Models and Mathematics in Life and Social Sciences) University of Surrey; £11,561; to K. Wells, A. Hilton, J. Kilner, R. Winsky-Sommerer.
  • Sponsor Award- Grant Seminar Competition 2010-2011, Institute of Advanced Studies, University of Surrey; £2,500 to R. Winsky-Sommerer & D-J Dijk. Two-day international workshop “Multidisciplinary Dissection of Sleep Phenotypes in Animals and Humans”, July 13-14, 2011
  • University of Surrey.Research Grant- Forschungskredit 2007 University of Zurich; FK2007#54321101; 2007-2009; CHF100,000; 24 months; to R. Winsky-Sommerer (PI).

Award(s) received

  • Award for Outstanding Basic Sleep Research 2009- Swiss Society of Sleep Research, Sleep Medicine and Chronobiology.

Publications

Journal articles

  • Zanos P, Wright SR, Georgiou P, Yoo JH, Hourani SM, Kitchen I, Winsky-Sommerer R, Bailey A, Ledent C. (2014) 'Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A receptor-independent mechanism'. Pharmacology Biochemistry and Behavior, 119, pp. 72-79.

    Abstract

    There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergic system is dysregulated following chronic methamphetamine administration. We tested this hypothesis by examining the effect of chronic methamphetamine administration on oxytocin receptor density in mice brains with the use of quantitative receptor autoradiographic binding. Saline (4 ml/kg/day, i.p.) or methamphetamine (1 mg/kg/day, i.p.) was administered daily for 10 days to male, CD1 mice. Quantitative autoradiographic mapping of oxytocin receptors was carried out with the use of [I]-vasotocin in brain sections of these animals. Chronic methamphetamine administration induced a region specific upregulation of oxytocin receptor density in the amygdala and hypothalamus, but not in the nucleus accumbens and caudate putamen. As there is evidence suggesting an involvement of central adenosine A receptors on central endogenous oxytocinergic function, we investigated whether these methamphetamine-induced oxytocinergic neuroadaptations are mediated via an A receptor-dependent mechanism. To test this hypothesis, autoradiographic oxytocin receptor binding was carried out in brain sections of male CD1 mice lacking A receptors which were chronically treated with methamphetamine (1 mg/kg/day, i.p. for 10 days) or saline. Similar to wild-type animals, chronic methamphetamine administration induced a region-specific upregulation of oxytocin receptor binding in the amygdala and hypothalamus of A receptor knockout mice and no genotype effect was observed. These results indicate that chronic methamphetamine use can induce profound neuroadaptations of the oxytocinergic receptor system in brain regions associated with stress, emotionality and social bonding and that these neuroadaptations are independent on the presence of A receptors. These results may at least partly explain some of the behavioural consequences of chronic methamphetamine use. © 2013 Elsevier Inc. All rights reserved.

  • Hasan S, van der Veen DR, Winsky-Sommerer R, Hogben A, Laing EE, Koentgen F, Dijk DJ, Archer SN. (2014) 'A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.'. FASEB J, 28 (6), pp. 2441-2454.

    Abstract

    In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) θ power during wakefulness and δ power during sleep, were greater in the Per3(5/5) mice. During recovery, the Per3(5/5) mice fully compensated for the SD-induced deficit in δ power, but the Per3(4/4) and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism.

  • Zanos P, Georgiou P, Wright SR, Hourani SM, Kitchen I, Winsky-Sommerer R, Bailey A. (2014) 'The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice'. Neuropsychopharmacology, 39 (4), pp. 855-865.

    Abstract

    The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse.

  • Zanos P, Georgiou P, Wright SR, Hourani SM, Kitchen I, Winsky-Sommerer R, Bailey A. (2013) 'The Oxytocin Analogue Carbetocin Prevents Emotional Impairment and Stress-Induced Reinstatement of Opioid-Seeking in Morphine-Abstinent Mice.'. Neuropsychopharmacology,

    Abstract

    The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse.Neuropsychopharmacology advance online publication, 4 December 2013; doi:10.1038/npp.2013.285.

  • Zanos P, Wright SR, Georgiou P, Yoo JH, Hourani SM, Kitchen I, Winsky-Sommerer R, Bailey A, Ledent C. (2013) 'Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A receptor-independent mechanism'. Pharmacology Biochemistry and Behavior,

    Abstract

    There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergic system is dysregulated following chronic methamphetamine administration. We tested this hypothesis by examining the effect of chronic methamphetamine administration on oxytocin receptor density in mice brains with the use of quantitative receptor autoradiographic binding. Saline (4 ml/kg/day, i.p.) or methamphetamine (1 mg/kg/day, i.p.) was administered daily for 10 days to male, CD1 mice. Quantitative autoradiographic mapping of oxytocin receptors was carried out with the use of [I]-vasotocin in brain sections of these animals. Chronic methamphetamine administration induced a region specific upregulation of oxytocin receptor density in the amygdala and hypothalamus, but not in the nucleus accumbens and caudate putamen. As there is evidence suggesting an involvement of central adenosine A receptors on central endogenous oxytocinergic function, we investigated whether these methamphetamine-induced oxytocinergic neuroadaptations are mediated via an A receptor-dependent mechanism. To test this hypothesis, autoradiographic oxytocin receptor binding was carried out in brain sections of male CD1 mice lacking A receptors which were chronically treated with methamphetamine (1 mg/kg/day, i.p. for 10 days) or saline. Similar to wild-type animals, chronic methamphetamine administration induced a region-specific upregulation of oxytocin receptor binding in the amygdala and hypothalamus of A receptor knockout mice and no genotype effect was observed. These results indicate that chronic methamphetamine use can induce profound neuroadaptations of the oxytocinergic receptor system in brain regions associated with stress, emotionality and social bonding and that these neuroadaptations are independent on the presence of A receptors. These results may at least partly explain some of the behavioural consequences of chronic methamphetamine use. © 2013 Elsevier Inc. All rights reserved.

  • Epelbaum J, Viollet C, Winsky-Sommerer R. (2013) 'Somatostatin/Cortistatin'. Handbook of Biologically Active Peptides, , pp. 933-942.
  • Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk DJ. (2012) 'Differential Effects of a Dual Orexin Receptor Antagonist (SB-649868) and Zolpidem on Sleep Initiation and Consolidation, SWS, REM Sleep, and EEG Power Spectra in a Model of Situational Insomnia.'. Nature Neuropsychopharmacology, England: 37 (5), pp. 1224-1233.

    Abstract

    Orexins have a role in sleep regulation, and orexin receptor antagonists are under development for the treatment of insomnia. We conducted a randomised, double-blind, placebo-controlled, four-period crossover study to investigate the effect of single doses of the dual orexin receptor antagonist SB-649868 (10 or 30 mg) and a positive control zolpidem (10 mg), an allosteric modulator of GABA(A) receptors. Objective and subjective sleep parameters and next-day performance were assessed in 51 healthy male volunteers in a traffic noise model of situational insomnia. Compared with placebo, SB-649868 10 and 30 mg increased total sleep time (TST) by 17 and 31 min (p<0.001), whereas after zolpidem TST was increased by 11.0 min (p=0.012). Wake after sleep onset was reduced significantly by 14.7 min for the SB-6489698 30 mg dose (p<0.001). Latency to persistent sleep was significantly reduced after both doses of SB-6489698 (p=0.003), but not after zolpidem. Slow wave sleep (SWS) and electroencephalogram (EEG) power spectra in non-REM sleep were not affected by either dose of SB-640868, whereas SWS (p< 0.001) and low delta activity (<=1.0 Hz) were increased, and 2.25-11.0 Hz activity decreased after zolpidem. REM sleep duration was increased after SB-649868 30 mg (p=0.002) and reduced after zolpidem (p=0.049). Latency to REM sleep was reduced by 20.1 (p=0.034) and 34.0 min (p<0.001) after 10 and 30 mg of SB-649868. Sleep-onset REM episodes were observed. SB-649868 was well tolerated. This dual orexin receptor antagonist exerts hypnotic activity, with effects on sleep structure and the EEG that are different from those of zolpidem.

  • Dijk D-J, Winsky-Sommerer R. (2012) 'Sleep: The way we snooze now'. New Scientist, 213 (2850)

    Abstract

    Light bulbs, television, computers and shift work have all altered sleeping habits. This has huge implications for sleep deprivation and our health. © 2012 Reed Business Information Ltd, England.

  • Dijk D-J, Winsky-Sommerer R. (2012) 'Sleep: Moving to a 24/7 society'. New Scientist, 213 (2850)

    Abstract

    The growing scientific interest in sleep, its organisation and recognition of its importance to health will transform how we approach it in the future. © 2012 Reed Business Information Ltd, England.

  • Dijk D-J, Winsky-Sommerer R. (2012) 'Sleep: How much we need and what keeps us awake'. New Scientist, 213 (2850)

    Abstract

    Recent research has brought new insights into our sleep requirements - from the amount we need to when, where and how we do it. © 2012 Reed Business Information Ltd, England.

  • Dijk D-J, Winsky-Sommerer R. (2012) 'Sleep: What it is and what it's for'. New Scientist, 213 (2850)

    Abstract

    Since the 1950s, sleep science has revealed much about its structure and patterns. Even so, its origins and functions remain largely mysterious. © 2012 Reed Business Information Ltd, England.

  • Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk D-J. (2012) 'Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia'. Neuropsychopharmacology, 37 (5), pp. 1224-1233.
  • Hasan S, van der Veen DR, Winsky-Sommerer R, Dijk DJ, Archer SN. (2011) 'Altered sleep and behavioral activity phenotypes in PER3-deficient mice.'. Am J Physiol Regul Integr Comp Physiol,

    Abstract

    Sleep homeostasis and circadian rhythmicity interact to determine the timing of behavioral activity. Circadian clock genes contribute to circadian rhythmicity centrally and in the periphery, but some also have roles within sleep regulation. The clock gene Period3 (Per3) has a redundant function within the circadian system and is associated with sleep homeostasis in humans. This study investigated the role of PER3 in sleep/wake activity and sleep homeostasis in mice by recording wheel running activity under baseline conditions in wild-type (WT; n = 54) and in PER3-deficient (Per3(-/-); n = 53) mice, as well as EEG-assessed sleep before and after 6 hours of sleep deprivation in WT (n = 7) and Per3(-/-) (n = 8) mice. Whereas total activity and vigilance states did not differ between the genotypes, the temporal distribution of wheel running activity, vigilance states, and EEG delta activity was affected by genotype. In Per3(-/-) mice, running wheel activity was increased and REM sleep and NREM sleep were reduced in the middle of the dark phase, and delta activity was enhanced at the end of the dark phase. At the beginning of the baseline light period, there was less wakefulness and more REM and NREM in Per3(-/-) mice. Per3(-/-) mice spent less time in wakefulness and more time in NREM sleep in the light period immediately after sleep deprivation and REM sleep accumulated more slowly during the recovery dark phase. These data confirm a role for PER3 in sleep/wake timing and sleep homeostasis.

  • Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, Winsky-Sommerer R, Semba K, Fredholm BB, Boison D, Hayaishi O, Urade Y, Chen JF. (2011) 'Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens.'. Society for Neuroscience J Neurosci, United States: 31 (27), pp. 10067-10075.

    Abstract

    Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A(2A)Rs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A(2A)Rs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A(2A)Rs were focally removed from the NAc core or other A(2A)R-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain.

  • Zanos P, Alshehri M, Sahabandu T, Winsky-Sommerer R, Kitchen I, Bailey A. (2011) 'Persistent brain region-specific upregulation of vasopressin (V1ar) and oxytocin receptors in chronic intermittent escalating dose morphine administration in mice'. POLISH ACAD SCIENCES INST PHARMACOLOGY PHARMACOL REP, 63 (1), pp. 252-252.
  • Palchykova S, Winsky-Sommerer R, Shen H-Y, Boison D, Gerling A, Tobler I. (2010) 'Manipulation of Adenosine Kinase Affects Sleep Regulation in Mice'. SOC NEUROSCIENCE JOURNAL OF NEUROSCIENCE, 30 (39), pp. 13157-13165.
  • Winsky-Sommerer R. (2009) 'Mechanisms Underlying the Effects of GABAA Sedative-Hypnotic Drugs'. KARGER NEUROPSYCHOBIOLOGY, 59 (4), pp. 248-249.
  • Winsky-Sommerer R. (2009) 'Role of GABA(A) receptors in the physiology and pharmacology of sleep'. WILEY-BLACKWELL EUROPEAN JOURNAL OF NEUROSCIENCE, 29 (9), pp. 1779-1794.
  • Palchykova S, Winsky-Sommerer R, Tobler I. (2009) 'Sleep Deprivation in the Dark Period Does Not Impair Memory in OF1 Mice'. TAYLOR & FRANCIS INC CHRONOBIOL INT, 26 (4), pp. 682-696.

    Abstract

    There is increasing evidence that sleep facilitates memory acquisition and consolidation. Moreover, the sleep-wake history preceding memory acquisition and retention as well as circadian timing may be important. We showed previously that sleep deprivation (SD) following learning in OF1 mice impaired their performance on an object recognition task. The learning task was scheduled at the end of the 12 h dark period and the test 24 h later. To investigate the influence of the prominent circadian sleep-wake distribution typical for rodents, we now scheduled the learning task at the beginning of the dark period. Wakefulness following immediately after the learning task was attained either by gentle interference (SD; n = 20) or by spontaneous wheel running (RW; n = 20). Two control groups were used: one had no RW throughout the experiment (n = 23), while the other group's wheel was blocked immediately after acquisition (n = 16), thereby preventing its use until testing. Recognition memory, defined as the difference in exploration of a novel and of familiar objects, was assessed 24 h later during the test phase. Motor activity and RW use were continuously recorded. Remarkably, performance on the object recognition task was not influenced by the protocols; the waking period following acquisition did not impair memory, independent of the method inducing wakefulness (i.e., sleep deprivation or spontaneous running). Thus, all groups explored the novel object significantly longer than the familiar ones during the test phase. Interestingly, neither the amount of rest lost during the SD interventions nor the amount of rest preceding acquisition influenced performance. However, the total amount of rest obtained by the control and SD mice subjected to acquisition at “dark offset” correlated positively (r = 0.66) with memory at test, while no such relationship occurred in the corresponding groups tested at dark onset. Neither the amount of running nor intermediate rest correlated with performance at test in the RW group. We conclude that interfering with sleep during the dark period does not affect object recognition memory consolidation.

  • Palchykova S, Gerling A, Winsky-Sommerer R, Tobler I. (2009) 'Sleep Regulation in Mice with Adenosine Metabolism Deficiency'. KARGER NEUROPSYCHOBIOLOGY, 59 (4), pp. 261-262.
  • Winsky-Sommerer R, Knapman A, Fedele DE, Schofield CM, Vyazovskiy VV, Rudolph U, Huguenard JR, Fritschy J-M, Tobler I. (2008) 'Normal sleep homeostasis and lack of epilepsy phenotype in GABA(A) receptor alpha 3 subunit-knockout mice'. PERGAMON-ELSEVIER SCIENCE LTD NEUROSCIENCE, 154 (2), pp. 595-605.
  • Vyazovskiy VV, Tobler I, Winsky-Sommerer R. (2007) 'Alteration of behavior in mice by muscimol is associated with regional electroencephalogram synchronization'. PERGAMON-ELSEVIER SCIENCE LTD NEUROSCIENCE, 147 (3), pp. 833-841.
  • Winsky-Sommerer R, Vyazovskiy VV, Homanics GE, Tobler I. (2007) 'The EEG effects of THIP (Gaboxadol) on sleep and waking are mediated by the GABA(A) delta-subunit-containing receptors'. WILEY-BLACKWELL EUROPEAN JOURNAL OF NEUROSCIENCE, 25 (6), pp. 1893-1899.
  • Conti B, Sanchez-Alavez M, Winsky-Sommerer R, Morale MC, Lucero J, Brownell S, Fabre V, Huitron-Resendiz S, Henriksen S, Zorrilla EP, de Lecea L, Bartfai T. (2006) 'Transgenic mice with a reduced core body temperature have an increased life span'. AMER ASSOC ADVANCEMENT SCIENCE SCIENCE, 314 (5800), pp. 825-828.
  • Palchykova S, Winsky-Sommerer R, Meerlo P, Durr R, Tobler I. (2006) 'Sleep deprivation impairs object recognition in mice'. ACADEMIC PRESS INC ELSEVIER SCIENCE NEUROBIOLOGY OF LEARNING AND MEMORY, 85 (3), pp. 263-271.
  • Epelbaum J, Winsky-Sommerer R. (2006) 'Brain Somatostatin-Related Peptides'. Handbook of Biologically Active Peptides, , pp. 645-654.

    Abstract

    This chapter focuses on brain somatostatin-related peptides. Somatostatin-14 was originally characterized as a hypothalamic neurohormone responsible for the inhibition of pituitary growth hormone secretion. In the mammalian brain, two genes encode for the prosomatostatin-derived peptides, somatostatin-14 and -28, and procortistatin-related ones, respectively. Somatotropin release inhibiting factor (SRIF) immunoreactivity is largely distributed in many neurons in mammalian brain, including the human brain. The highest levels are found in the mediobasal hypothalamus and median eminence, amygdala, preoptic area, accumbens nucleus, cerebral cortex, striatum olfactory regions, and brain stem. SRIF mediates its biological functions via at least six receptor subtypes, termed sstl, sst2A, sst2B, sst3, sst4, and sst5, which all belong to the family of seven transmembrane domain G-protein-coupled receptors. With the noticeable exception of sst4, all subtypes do internalize in various cellular models following agonist treatment. In the brain, this has only been shown in vivo for the sst2 receptor. Although the sst2 receptor is the candidate likely to mediate the anticonvulsant effects of SRIF in the rat hippocampus, in the mouse hippocampus recent observations support a central role of sst4 and/or sst1 receptors in mediating SRIF inhibition of epileptiform activity. © 2006 Elsevier Inc. All rights reserved.

  • Winsky-Sommerer R, Boutrel B, de Lecea L. (2005) 'Stress and arousal - The corticotrophin-releasing factor/hypocretin circuitry'. HUMANA PRESS INC MOL NEUROBIOL, 32 (3), pp. 285-294.

    Abstract

    The hypocretins (also know as orexins) are two neuropeptides now commonly described as critical components for maintaining and regulating the stability of arousal. Several lines of evidence have raised the hypothesis that hypocretin-producing neurons are part of the circuitries that mediate the hypothalamic response to acute stress. New data indicate that the corticotrophin-releasing factor (CRF) peptidergic system directly innervates hypocretin-expressing neurons. CRF depolarizes hypocretin neurons, and this effect is blocked by a CRF-R1 antagonist. Furthermore, activation of hypocretinergic neurons by stress is impaired in CRF-R1 knockout mice. These data suggest that CRF-R1 receptor mediates the stress-induced activation of the hypocretinergic system. A significant amount of evidence also indicates that hypocretin cells connect reciprocally to the CRF system. We propose that upon stressor stimuli, CRF activates the hypocretin system, which relays these signals to brain stem nuclei involved in the modulation of arousal as well as to the extended amygdala, a structure involved in the negative motivational state that drives addiction.

  • Urena JM, La Torre A, Martinez A, Lowenstein E, Franco N, Winsky-Sommerer R, Fontana X, Casaroli-Marano R, Ibanez-Sabio MA, Pascual M, Del Rio JA, de Lecea L, Soriano E. (2005) 'Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain'. WILEY-LISS JOURNAL OF COMPARATIVE NEUROLOGY, 490 (2), pp. 119-132.
  • Levine AS, Winsky-Sommerer R, Huitron-Resendiz S, Grace MK, de Lecea L. (2005) 'Injection of neuropeptide W into paraventricular nucleus of hypothalamus increases food intake'. AMER PHYSIOLOGICAL SOC AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 288 (6), pp. R1727-R1732.
  • Paneda C, Winsky-Sommerer R, Boutrel B, de Lecea L. (2005) 'The corticotropin-releasing factor-hypocretin connection: Implications in stress response and addiction'. PROUS SCIENCE, SA DRUG NEWS PERSPECT, 18 (4), pp. 250-255.

    Abstract

    The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. Recent data have raised the hypothesis that hypocretin neurons are also part of the circuitries that mediate the hypothalamic stress response. In particular, we have recently demonstrated that corticotrophin-releasing factor (CRF)immunoreactive terminals make direct synaptic contacts with hypocretin-expressing neurons and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. Furthermore, CRF excites hypocretinergic cells ex vivo through CRF-R1 receptors. Activation of hypocretinergic neurons in response to acute stress is severely impaired in CRF-R1 knockout mice. Moreover, the stress response is impaired in hypocretin-deficient mice. We propose that upon stressor stimuli, CRF stimulates the release of hypocretins, and this circuit contributes to activation and maintenance of arousal associated with the stress response and addiction. (c) 2005 Prous Science. All rights reserved.

  • Conti B, Sugama S, Lucero J, Winsky-Sommerer R, Wirz SA, Maher P, Andrews Z, Barr AM, Morale MC, Paneda C, Pemberton J, Gaidarova S, Behrens MM, Beal F, Sanna PP, Horvath TL, Bartfai T. (2005) 'Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl-phenyl-tetrahydropyridine toxicity'. BLACKWELL PUBLISHING LTD JOURNAL OF NEUROCHEMISTRY, 93 (2), pp. 493-501.
  • Winsky-Sommerer R, Yamanaka A, Diano S, Borok E, Roberts AJ, Sakurai T, Kilduff TS, Horvath TL, de Lecea L. (2004) 'Interaction between the corticotropin-releasing factor system and hypocretins (Orexins): A novel circuit mediating stress response'. SOC NEUROSCIENCE JOURNAL OF NEUROSCIENCE, 24 (50), pp. 11439-11448.
  • Winsky-Sommerer R, Spier AD, Fabre V, de Lecea L, Criado JR. (2004) 'Overexpression of the human beta-amyloid precursor protein downregulates cortistatin mRNA in PDAPP mice'. ELSEVIER SCIENCE BV BRAIN RESEARCH, 1023 (1), pp. 157-162.
  • Winsky-Sommerer R, Boutrel B, de Lecea L. (2003) 'The role of the hypcretinergic system in the integration of networks that dictate the states of arousal'. PROUS SCIENCE, SA DRUG NEWS PERSPECT, 16 (8), pp. 504-512.

    Abstract

    Recent studies have led to the discovery of a neuropeptide system that regulates arousal states, The hypocretins (hcrt1 and hcrt2, also called the orexins) are neuropeptides of related sequence derived from the same precursor whose expression is restricted to a few thousand neurons of the lateral hypothalamus. Two G-protein-coupled receptors for the hypocretins have been identified, and these have different distributions within the central nervous system and differential affinities for the two hypocretins. Hypocretin fibers project throughout the brain, including several areas implicated in cardiovascular function and regulation of the sleep-wake cycle. Central administration of synthetic hypocretin-1 affects blood pressure, hormone secretion and locomotor activity, and increases wakefulness while suppressing rapid eye movement sleep. Most human patients with narcolepsy have greatly reduced levels of hypocretin peptides in their cerebral spinal fluid and no or barely detectable hypocretin neurons in their hypothalami, suggestive of autoimmune attack. Development of nonpeptidergic hypocretin antagonists may prove useful in sleep disorders, whereas hypocretin agonists may be used to treat narcolepsy and excessive daytime sleepiness. The hypocretins are also an excellent target for the pharmacological treatment of the deregulated arousal state that characterizes depression or addictive behavior. (C) 2003 Prous Science. All rights reserved.

  • Winsky-Sommerer R, Grouselle D, Rougeot C, Laurent V, David JP, Delacourte A, Dournaud P, Seidah NG, Lindberg I, Trottier S, Epelbaum J. (2003) 'The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease'. PERGAMON-ELSEVIER SCIENCE LTD NEUROSCIENCE, 122 (2), pp. 437-447.
  • Cervera P, Videau C, Viollet C, Petrucci C, Lacombe J, Winsky-Sommerer R, Csaba Z, Helboe L, Daumas-Duport C, Reubi JC, Epelbaum J. (2002) 'Comparison of somatostatin receptor expression in human gliomas and medulloblastomas'. BLACKWELL PUBLISHING LTD JOURNAL OF NEUROENDOCRINOLOGY, 14 (6), pp. 458-471.
  • Grouselle D, Winsky-Sommerer R, David JP, Delacourte A, Dournaud P, Epelbaum J. (1998) 'Loss of somatostatin-like immunoreactivity in the frontal cortex of Alzheimer patients carrying the apolipoprotein epsilon 4 allele'. ELSEVIER SCI IRELAND LTD NEUROSCIENCE LETTERS, 255 (1), pp. 21-24.

Conference papers

  • Abásolo D, Winsky-Sommerer R. (2013) 'Investigating the possible usefulness of Lempel-Ziv complexity for the characterisation of electroencephalogram sleep recordings'. Final Programme and Book of Abstracts of BioDynamics 2013, Bristol, UK: BioDynamics 2013 - Rhythms in biological systems, pp. 24-25.
  • Hasan S, Winsky-Sommerer R, Dijk D-J, Archer SN. (2012) 'Sleep in transgenic mouse models for a polymorphism in the human PER3 gene'. WILEY-BLACKWELL JOURNAL OF SLEEP RESEARCH, Paris, FRANCE: 21st Congress of the European-Sleep-Research-Society 21, pp. 79-79.
  • Kovacs Z, Tobler I, Winsky-Sommerer R. (2009) 'Role of the GABAA Alpha4-Subtype in Sleep and Sleep Regulation'. Neuropsychobiology: international journal of experimental and clinical research in biological psychiatry, pharmacopsychiatry, biological psychology, pharmacopsychology and pharmacoelectroencephalography, Annual Conference of Swiss Society of Sleep Research, Sleep Medicine and Chronobiology 4 (59), pp. 267-267.
  • Kovacs Z, Tobler I, Winsky-Sommerer R. (2009) 'DECIPHERING THE ROLE OF THE GABA-A ALPHA4-SUBTYPE IN SLEEP'. AMER ACAD SLEEP MEDICINE SLEEP, Seattle, WA: 23rd Annual Meeting of the Associated-Professional-Sleep-Societies 32, pp. A14-A15.
  • Winsky-Sommerer R. (2008) 'New insights from basic animal research on GABAA receptor mediated inhibition to understand selective pharmacological profiles of hypnotics'. WILEY-BLACKWELL PUBLISHING, INC JOURNAL OF SLEEP RESEARCH, Glasgow, SCOTLAND: 19th Congress of the European-Sleep-Research-Society 17, pp. 58-58.
  • Kovacs Z, Tobler I, Winsky-Sommerer R. (2008) 'A role for GABAA alpha 4-subunit-containing receptors in sleep regulation?'. WILEY-BLACKWELL PUBLISHING, INC JOURNAL OF SLEEP RESEARCH, Glasgow, SCOTLAND: 19th Congress of the European-Sleep-Research-Society 17, pp. 203-204.
  • Winsky-Sommerer R, Knapman A, Tobler I. (2008) 'Sleep and sleep regulation in mice lacking the GABA-A receptor A3-subunit'. AMER ACAD SLEEP MEDICINE SLEEP, Baltimore, MD: 22nd Annual Meeting of the Associated-Professional-Sleep-Societies 31, pp. A17-A18.
  • Winsky-Sommerer R, Tobler I. (2006) 'Evidence for mechanism of action of the GABA-A receptor agonist THIP in GABA-A receptor delta subunit knockout mice'. BLACKWELL PUBLISHING JOURNAL OF SLEEP RESEARCH, Innsbruck, AUSTRIA: 18th Congress of the European-Sleep-Research-Society 15, pp. 238-238.
  • Winsky-Sommerer R, Vesely M, Tobler I. (2006) 'Effects of the GABA-A receptor agonist THIP on the sleep EEG of GABA-A receptor delta subunit knockout mice'. AMER ACADEMY SLEEP MEDICINE SLEEP, Salt Lake City, UT: 20th Annual Meeting of the Associated-Professional-Sleep-Societies 29, pp. A21-A21.
  • Boutrel B, Kenny PJ, Specio SS, Winsky-Sommerer R, Halfon O, Magistretti PJ, Markou A, Koob GF, de Lecea L. (2005) 'A key role for hypocretin in regulating brain reward function and reinstatement for drug-seeking behavior in rats'. LIPPINCOTT WILLIAMS & WILKINS BEHAVIOURAL PHARMACOLOGY, Barcelona, SPAIN: 11th Biennial Meeting of the European-Behavioral-Pharmacology-Society 16, pp. S60-S60.
  • de Lecea L, Winsky-Sommerer R, Suzuki C, Xu Y, Reinscheid R. (2005) 'Neuropeptide S projects to arousal nuclei'. AMER ACADEMY SLEEP MEDICINE SLEEP, Denver, CO: 19th Annual Meeting of the Associated-Professional-Sleep-Societies 28, pp. A10-A10.
  • Huitron-Resendiz S, Winsky-Sommerer R, Sanchez-Alavez M, Wills DN, Xu Y, Civelli O, Henriksen SJ, Criado JR, Reinscheid RK, de Lecea L. (2004) 'Effects of neuropeptide S in the regulation of sleep-wake cycle'. AMER ACADEMY SLEEP MEDICINE SLEEP, Philadelphia, PA: 18th Annual Meeting of the Associated-Professional-Sleep-Societies 27, pp. 32-33.
  • Winsky-Sommerer R, Yamanaka A, Sakurai T, Roberts AJ, Kilduff TS, de Lecea L. (2004) 'Interaction between the corticotropin-releasing-factor system and hypocretins: Components mediating the stress response'. AMER ACADEMY SLEEP MEDICINE SLEEP, Philadelphia, PA: 18th Annual Meeting of the Associated-Professional-Sleep-Societies 27, pp. 23-23.
  • Winsky-Sommerer R, Huitron-Resendiz S, Sanchez-Alavez M, Slaght K, Henriksen SJ, Criado JR, de Lecea L. (2003) 'Effect of the endogenous GPR7/8 ligand (neuropeptide W) on sleep/wakefulness'. AMER ACADEMY SLEEP MEDICINE SLEEP, CHICAGO, ILLINOIS: 17th Annual Meeting of the Associated-Professional-Sleep-Societies 26, pp. A49-A49.
  • Huitron-Resendiz S, Clark SD, Sanchez-Alavez M, Winsky-Sommerer R, Civelli O, Nothacker HP, Henriksen SJ, Criado JR, de Lecea L. (2003) 'Effects of urotensin-II in the regulation of REM sleep'. AMER ACADEMY SLEEP MEDICINE SLEEP, CHICAGO, ILLINOIS: 17th Annual Meeting of the Associated-Professional-Sleep-Societies 26, pp. A47-A48.

Teaching

BMS1023 Chemistry & Mathematics for the Biosciences
BMS1030 Biochemistry
BMS2033 Analytical Biochemistry & Chemistry
BMS2046 Pathology and Medicine
BMS3055 Pharmacology 2
BMS3064 Neuroscience 2 - Module organiser
MSc Clinical Biochemistry

Supervision of research students (BSc, MSc and PhD students)

Departmental Duties

  • Divisional Representative on the Faculty of Health & Medical Sciences Ethics Committee (since 2010)
  • Organiser of external (national and international) speakers for the monthly Sleep, Chronobiology & Neurodisorders Theme meetings (since 2010)

Affiliations

European Sleep Research Society (ESRS) - Coordinator of the ESRS forum for Women in Sleep Research
Sleep Research Society (SRS)
FENS (Federation of European Neuroscience Societies)
British Neuroscience Society (BNA) 

Page Owner: rw0012
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Last Modified: Tuesday 9 October 2012 08:31:39 by rw0012
Expiry Date: Thursday 13 January 2011 14:16:52
Assembly date: Fri Jul 25 02:35:56 BST 2014
Content ID: 16474
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