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