Respiratory, sleep and metabolic disorders associated with the obstructive sleep apnea syndrome; homeostatic regulation of sleep
Hypoventilations and apneas characteristic of the Obstructive Sleep Apnea Syndrome (OSAS) occur most frequently and are most severe during the desynchronized, rapid eye movement (REM) stage of sleep. The resulting loss of sleep further exacerbates the disorder. The goals of our research are to understand the pharmacological mechanisms of REM sleep and the accompanying suppression of motoneuronal activity, and to identify the cellular basis of the response to sleep deprivation. Due to the complex nature of sleep, we use complementary electrophysiological in vivo and in vitro techniques, neuroanatomy and molecular biology. In electrophysiological studies, we use a novel pharmacological model of REM sleep. To characterize the role of different neurotransmitter receptors in sleep-related disorders of breathing, we use in vivo pharmacology and, separately, study changes in receptor mRNA expression in brain regions and single cells involved in the regulation of sleep and breathing. Since OSAS frequently coexists with the metabolic syndrome (hypertension, obesity and diabetes), we also investigate whether oscillation in blood oxygen level (chronic intermittent hypoxia) cause changes in the central and peripheral control of glucose metabolism, such as in type 2 diabetes. We pursue our hypothesis that prolonged wakefulness leads to increased expression of GABAA receptors in the posterior hypothalamus, a region in which increased GABAergic inhibition acts to promote sleep.
Immunohistochemistry and tract-tracing; gene expression analysis; single-cell RT-PCR; intra- and extracellular recording in vivo; iontophoresis and microinjections; behavioral analysis of sleep/movement in rodents
Fenik VB, Singletary T, Branconi JL, Davies RO, Kubin L Glucoregulatory consequences and cardiorespiratory parameters in rats exposed to chronic-intermittent hypoxia: effects of the duration of exposure and losartan. Frontiers in Neurology 3: 1-13, 2012.Stettner GM, Fenik VB, Kubin L Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons. Journal of Applied Physiology 112: 305-312, 2012.Brandes IF, Stettner GM, Mörschel M, Kubin L, Dutschmann M REM sleep-like episodes of motoneuronal depression and respiratory rate increase are triggered by pontine carbachol microinjections in in situ perfused rat brainstem preparation. Experimental Physiology 96: 548-555, 2011.Mody P, Rukhadze I, Kubin L Rats subjected to chronic-intermittent hypoxia have increased density of noradrenergic terminals in the trigeminal sensory and motor nuclei. Neuroscience Letters 505: 176-179, 2011.Stettner GM, Kubin L, Volgin DV Antagonism of orexin 1 receptors eliminates motor hyperactivity and improves homing response acquisition in juvenile rats exposed to alcohol during early postnatal period. Behavioural Brain Research 221: 324-328, 2011.Rukhadze I, Kamani H, Kubin L Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain. Archives Italiennes de Biologie 149: 499-515, 2011.Rukhadze I, Fenik VB, Benincasa KE, Price A, Kubin L Chronic intermittent hypoxia alters density of aminergic terminals and receptors in the hypoglossal motor nucleus. American Journal of Respiratory and Critical Care Medicine 182: 1321-1329, 2010.Lu JW, Kubin L Electromyographic activity at the base and tip of the tongue across sleep-wake states in rats. Respiratory Physiology & Neurobiology 167: 307-315, 2009.Kubin L Adventures and tribulations in the search for the mechanisms of the atonia of REM sleep. Sleep 31: 1473-1476, 2008.Kubin L, Volgin DV Developmental profiles of neurotransmitter receptors in respiratory motor nuclei. Respiratory Physiology & Neurobiology 164: 64-71, 2008.Fenik VB, Rukhadze I, Kubin L Inhibition of pontine noradrenergic A7 cells reduces hypoglossal nerve activity in rats. Neuroscience 157: 473-482, 2008.Rukhadze I, Fenik VB, Branconi JL, Kubin L Fos expression in pontomedullary catecholaminergic cells following rapid eye movement sleep-like episodes elicited by pontine carbachol in urethane-anesthetized rats. Neuroscience 152: 208-222, 2008.Volgin DV, Rukhadze I, Kubin L Hypoglossal premotor neurons of the intermediate medullary reticular region express cholinergic markers. Journal of Applied Physiology 105: 1576-1584, 2008.Lu JW, Fenik VB, Branconi JL, Mann GL, Rukhadze I, Kubin L Disinhibition of perifornical hypothalamic neurones activates noradrenergic neurones and blocks pontine carbachol-induced REM sleep-like episodes in rats. Journal of Physiology 582: 553-567, 2007.Fenik VB, Davies RO, Kubin L REM sleep-like atonia of hypoglossal (XII) motoneurons is caused by loss of noradrenergic and serotonergic inputs.[see comment]. American Journal of Respiratory & Critical Care Medicine 172: 1322-1330, 2005.
Ph.D. (Physiology) Warsaw School of Medicine, 1983Ph.D. (Neurophysiology) Scuola Normale Superiore, Pisa, Italy, 1983MS (Biomedical Engineering) Warsaw Polytechnic, 1976Docent (Neuropharmacology) Center of Experimental and Clinical Medicine, Polish Academy of Sciences, Warsaw, 2000