Neurogenetics of Sleep

Max Planck Institute of Psychiatry

Contact:
Mayumi Kimura
Position:
Group Leader
Address:
Kraepelinstrasse 2 - 10, 80804
City:
Munich
Country:
Germany
Phone:
+49 89 30622 549
Fax:
+49 89 30622 610
Contact E-mail:
Research Domain
Keywords

Laboratory description

Our research focuses on genes or gene products that contribute to sleep-wake regulation or sleep disorders. Manipulating gene activity can affect a structure of sleep patterns and would be able to provide us models for studying the mechanism of disturbed sleep. To monitor such possibilities, we are efficiently equipped to analyze spontaneous sleep-wake behavior of unrestrained mice from continuous EEG and EMG recordings. In correlation with alterations in sleep patterns, we also investigate an influence of endocrine factors and neurotransmitter changes.

The Max Planck Institute of Psychiatry, we have access to a wide-variety of gene-manipulated or selectively bred mouse models that exhibit or concern psychiatry/neurological diseases. Based on monitoring EEG-EMG polysomnogram, we investigate which animal models display impaired sleep-wake behavior and then post-genomically evaluate the function of genes or gene products for sleep, using conventional as well as tissue-specific conditional transgenic mice or stress-vulnerable strains. Sleep disturbances are the most significant symptom that develops in association with depression. Noticing and curing distracted sleep patterns may be of help preventing progress of the disease. Our research group preclinically investigates particular sleep alterations in those models and distinguishes, if possible, sleep-impairing causality from that of depression.


Technical Capabilities and areas of expertise

Sleep recordings in mice, microdialysis, immunohistochemistry, RIA, in situ hybridization, emotional behavior phenotyping


Additional Descriptors, Keywords

Stress, depression, sleep disorders, mouse models, transgenic mice, HPA axis, corticotropin-releasing hormone, sleep deprivation, biomarkers


Selected Publications in the 5 past years:

Albu S, Romanowski CPN, Curzi ML, Jakubcakova V, Flachskamm C, Gassen NC, Hartmann J, Schmidt MV, Schmidt U, Rein T, Holsboer F, Hausch F, Paez-Pereda M, Kimura M. (2013) Deficiency of FK506-binding protein (FKBP) 51 alters sleep architecture and recovery sleep responses to stress in mice. Journal of Sleep Research in press.

Dresler M, Spoormaker VI, Beitinger P, Czisch M, Kimura M, Steiger A, Holsboer F. (2013) Neuroscience-driven discovery and development of sleep therapeutics. Pharmacology and Therapeutics, doi: 10.1016/j.pharmthera.2013.10.012.

Jakubcakova V, Curzi ML, Flachskamm C, Hambsch B, Landgraf R, Kimura M. (2013) The glycolytic metabolite methylglyoxal induces changes in vigilance by generating low-amplitude non-REM sleep. Journal of Psychopharmacology, 27:1070-1075.

Polta SA, Fenzl T, Jakubcakova V, Kimura M, Yassouridis A, Wotjak CT. (2013) Prognostic and symptomatic aspects of rapid eye movement sleep in a mouse model of posttraumatic stress disorder. Frontiers in Behavioral Neuroscience, doi: 10.3389/fnbeh.2013.00060.

Jakubcakova V, Flachskamm C, Landgraf R, Kimura M. (2012) Sleep phenotyping in a mouse model of extreme trait anxiety. PLoS One. 7:e40625.

Dedic N, Touma C, Romanowski CP, Schieven M, Kühne C, Ableitner M, Lu A, Holsboer F, Wurst W, Kimura M, Deussing JM. (2012) Assessing behavioural effects of chronic HPA axis activation using conditional CRH-overexpressing mice. Cellular and Molecular Neurobiology, 32:815-828.

Kimura M, Ohl F. (2012) Schlaf-EEG bei Mäusen und Ratten. In: Handbuch der Pharmakotherapie, 2. Auflage (eds. Gründer, G. and Benkert, O.), pp.219-132, Springer-Verlag GmbH, Berlin Heidelberg.

Kimura M (2012) Sex hormones and sleep. Japanese Journal of Sleep Medicine, 6:411-418.

Jakubcakova V, Flachskamm C, Deussing JM, Kimura M. (2011) Deficiency of corticotropin-releasing hormone type-2 receptor alters sleep responses to bacterial lipopolysaccharide in mice. Brain, Behavior, and Immunity, 25:1626-1636.

Sakakibara H, Romanowski CNP, Jakubcakova V, Flachskamm C, Shimoi K, Kimura M. (2011) Feeble awake effects of plasminogen activator inhibitor type-1 in mice. Behavioural Brain Research, 220:354-357.

Fenzl T, Romanowski CPN, Flachskamm C, Deussing J, Kimura M. (2011) Wake-promoting effects of orexin: its independent actions against the background of an impaired corticotropine-releasing hormone receptor system. Behavioural Brain Research, 222:43-50.

Fenzl T, Touma C, Romanowski CPN, Ruschel J, Holsboer F, Landgraf R, Kimura M, Yassouridis A. (2011) Sleep disturbances in highly stress reactive mice: Modeling endophenotypes of major depression. BMC Neuroscience, 12:29.

Winkelmann, J, Kimura M. (2011) Genetics of sleep disorders.In: Handbook of Clinical Neurology, 3rd Series, Volume 99 Sleep Disorders Part II (eds. Montagna, P. and Chokroverty, S.), pp.681-693, Elsevier BV, Amsterdam.

Steiger A, Kimura M (2010) Hormones and insomnia. In: Melatonin, Sleep and Insomnia, Endocrinology research and clinical development (ed. Soriento, Y. E.), pp. 205-226, Nova Science Publishers, New York.

Kimura M (2010) Hormones and sleep. In: Ethology of the brain and hormones – Invitation to behavioral neuroendocrinology (ed. Japanese Society for Behavioral Neuroendocrinology), pp. 190-203, Nishimura Co., Ltd., Tokyo. (in Japanese)

Steiger A, Kimura M. (2010) Pathophysiology of changes in sleep EEG and hormone secretion. In: Sleep and mental illness (eds. Pandi-Perumal, S. R. and Kramer, M.), pp.83-94, Cambridge University Press, Cambridge.

Romanowski CPN, Fenzl T, Falchskamm C, Wurst W, Holsboer F, Deussing JM, Kimura M (2010) Central deficiency of corticotropin-releasing hormone receptor type 1(CRH-R1) abolishes effects of CRH on NREM but not on REM sleep in mice. Sleep 33:427-436.

Kimura M, Müller-Preuss P, Lu A, Wiesner E, Flachskamm F, Wurst W, Holsboer F, Deussing JM (2010) Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep. Molecular Psychiatry 15:154-165.

Steiger A, Kimura M (2010) Wake and sleep EEG provide biomarkers in depression. Journal of Psychiatric Research 44:242-252.

Romanowski CPN, Fenzl T (2010) Automated sleep deprivation as a powerful tool for basic sleep research in animal models of affective disorders. In: Sleep deprivation: Causes, effects and treatments (eds. Fulke, P. and Vaughan, S. ), pp.257-70. Nova Science Publishers, New York.

Kimura M (2009) Stress, sleep, and CRH. Frontiers in Neuroscience 3:414.

Fenzl T, Flachskamm C, Rossbauer M, Deussing JM, and Kimura M (2009) Circadian rhythms of basal orexin levels in the hypothalamus are not influenced by an impaired corticotropin-releasing hormone receptor type 1 system. Behavioural Brain Research 203:143-145.

Touma C, Fenzl T, Ruschel J, Palme R, Holsboer F, Kimura M, and Landgraf R (2009) Rhythmicity in mice selected for extremes in stress reactivity: Behavioural, endocrine and sleep changes resembling endophenotypes of major depression. PloS One 4:e4325 doi:10.1371/journal.pone.0004325.

Kimura M (2009) Sleep and host defense mechanisms. Somnology (ed. Japanese Society of Sleep Research), pp. 201-7, Asakura Publishing, Tokyo. (in Japanese)


Key Publications of the Laboratory:

Jakubcakova V, Flachskamm C, Landgraf R, Kimura M. (2012) Sleep phenotyping in a mouse model of extreme trait anxiety. PLoS One. 7:e40625

Fenzl T, Romanowski CPN, Flachskamm C, Deussing J, Kimura M. (2011) Wake-promoting effects of orexin: its independent actions against the background of an impaired corticotropine-releasing hormone receptor system. Behavioural Brain Research, 222:43-50.

Romanowski CPN, Fenzl T, Falchskamm C, Wurst W, Holsboer F, Deussing JM, Kimura M (2010) Central deficiency of corticotropin-releasing hormone receptor type 1(CRH-R1) abolishes effects of CRH on NREM but not on REM sleep in mice. Sleep 33:427-436.

Kimura M, Müller-Preuss P, Lu A, Wiesner E, Flachskamm F, Wurst W, Holsboer F, Deussing JM (2010) Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep. Molecular Psychiatry 15:154-165.

Steiger A, Kimura M (2010) Wake and sleep EEG provide biomarkers in depression. Journal of Psychiatric Research 44:242-252.

Kimura M (2009) Stress, sleep, and CRH. Frontiers in Neuroscience 3:414.

Touma C, Fenzl T, Ruschel J, Palme R, Holsboer F, Kimura M, and Landgraf R (2009) Rhythmicity in mice selected for extremes in stress reactivity: Behavioural, endocrine and sleep changes resembling endophenotypes of major depression. PloS One 4:e4325 doi:10.1371/journal.pone.0004325.

Fenzl T, Romanowski CPM, Flachskamm C, Honsberg H, Boll E, Höhne A, Kimura, M (2007) Fully automataed sleep deprivation in mice as a tool in sleep research. J. Neuroscience Methods 166:229-235.

Kimura M, Winkelmann J (2007) Genetics of sleep and sleep disorders. Cellular and Molecular Life Sciences 64:1216-1226.


Current/Completed Grants (past 5 years):

EU Grant Frame 7 HEALTH, “Maintaining health in old age through homeostasis”, 2011-2015.


Other laboratory Members

Title:  PhD

Name:  Christoph Romanowski

Position:  post-doc

Email:  roma@mpipsykl.mpg.de

Title:  PhD

Name:  Deependra Kumar

Position:  Post-doc

Email:  deependra_kumar@mpipsykl.mpg.de

Title:  MSc

Name:  Mary Gazea

Position:  PhD student

Email:  gazea@mpipsykl.mpg.de

Name:  Cornelia Flachskamm

Position:  TA

Email:  flachsk@mpipsykl.mpg.de

Name:  Staphanie Voule

Position:  TA

Email:  alam@mpipsykl.mpg.de


Past Members

Title:  MSc

Name:  Maria Letizia Curzi

Position:  PhD student

Title:  PhD

Name:  Vladimira Jakubcakova

Position:  post-doc

Title:  BSc

Name:  Stefana Albu

Position:  Fulbright fellow

Title:  BSc

Name:  Anna Truckenbrodt

Position:  master student

Title:  PhD

Name:  Thomas Fenzl

Position:  post-doc

Title:  MD

Name:  Mira Dalal

Position:  post-doc

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