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
Boyle Caroline E, Parkar Anjum, Barror Amanda, Kubin Leszek: Noradrenergic terminal density varies among different groups of hypoglossal premotor neurons.[PMID 31128245] Journal of chemical neuroanatomy 100: 101651, May 2019.
Das Rajat K, Herr Kate B, Parkar Anjum, Kubin Leszek: Increased tongue use enhances 5-HT receptor immunostaining in hypoglossal motor nucleus.[PMID 30447306] Respiratory physiology & neurobiology 260: 105-113, 02 2019.
Herr Kate B, Mann Graziella L, Kubin Leszek: Modulation of Motoneuronal Activity With Sleep-Wake States and Motoneuronal Gene Expression Vary With Circadian Rest-Activity Cycle.[PMID 30131680] Frontiers in integrative neuroscience 12: 32, 2018.
Kubin Leszek, Mann Graziella L: Hypoglossal motoneurons are endogenously activated by serotonin during the active period of circadian cycle. [PMID 29129751] Respiratory physiology & neurobiology 248: 17-24, 01 2018.
Hicks Amelia, Cori Jennifer M, Jordan Amy S, Nicholas Christian L, Kubin Leszek, Semmler John G, Malhotra Atul, McSharry David G P, Trinder John A: Mechanisms of the deep, slow-wave, sleep-related increase of upper airway muscle tone in healthy humans.[PMID 28255086] Journal of applied physiology (Bethesda, Md. : 1985) 122(5): 1304-1312, May 2017.
Kubin Leszek: Neural Control of the Upper Airway: Respiratory and State-Dependent Mechanisms.[PMID 27783860] Comprehensive Physiology 6(4): 1801-1850, 09 2016.
Laitman, Benjamin M. Gajewski, Nicholas D. Mann, Graziella L. Kubin, Leszek. Morrison, Adrian R. Ross, Richard J.: The alpha1 adrenoceptor antagonist prazosin enhances sleep continuity in fear-conditioned Wistar-Kyoto rats.[PMID 24246572] Progress in Neuro-Psychopharmacology & Biological Psychiatry 49: 7-15, Mar 3 2014.
Rukhadze Irma, Kalter Julie, Stettner Georg M, Kubin Leszek: Lingual muscle activity across sleep-wake States in rats with surgically altered upper airway.[PMID 24803913] Frontiers in neurology 5: 61, 2014.
Kubin, L.: Sleep-wake control of the upper airway by noradrenergic neurons, with and without intermittent hypoxia.[PMID 24746052] Progress in Brain Research. Holstege, G., Beers, C.M., Subramanian, H.H. (Eds.), Volume titled: "The Central Nervous System Control of Respiration". (eds.). Elsevier, Amsterdam. 209: 255-274, 2014.
Rukhadze, I., Kalter, J., Stettner, G.M., Kubin, L.: Lingual muscle activity across sleep-wake states in rats with surgically altered upper airway.[PMID 24803913]
Frontiers in Neurology 5(61): 1-14, April 2014.
Volgin, Denys V. Lu, Jackie W. Stettner, Georg M. Mann, Graziella L. Ross, Richard J. Morrison, Adrian R. Kubin, Leszek.: Time- and behavioral state-dependent changes in posterior hypothalamic GABAA receptors contribute to the regulation of sleep. [PMID 24466145] PLoS ONE [Electronic Resource] 9(1): e86545, 2014.
Volgin, Denys V. Stettner, Georg M. Kubin, Leszek.: Circadian dependence of receptors that mediate wake-related excitatory drive to hypoglossal motoneurons.[PMID 23665050] Respiratory Physiology & Neurobiology 188(3): 301-7, Sep 15 2013.
Stettner, Georg M. Kubin, Leszek.: Antagonism of orexin receptors in the posterior hypothalamus reduces hypoglossal and cardiorespiratory excitation from the perifornical hypothalamus.[PMID 23104701] Journal of Applied Physiology 114(1): 119-30, Jan 1 2013.
Herr, Kate Benincasa. Stettner, Georg M. Kubin, Leszek.: Reduced c-Fos expression in medullary catecholaminergic neurons in rats 20 h after exposure to chronic intermittent hypoxia.[PMID 23364524] American Journal of Physiology - Regulatory Integrative & Comparative Physiology 304(7): R514-22, Apr 1 2013.
Stettner, Georg M. Lei, Yanlin. Benincasa Herr, Kate. Kubin, Leszek.: Evidence that adrenergic ventrolateral medullary cells are activated whereas precerebellar lateral reticular nucleus neurons are suppressed during REM sleep.[PMID 23630631] PLoS ONE [Electronic Resource] 8(4): e62410, 2013.
Stettner, Georg M. Kubin, Leszek. Volgin, Denys V.: Loss of motoneurons in the ventral compartment of the rat hypoglossal nucleus following early postnatal exposure to alcohol.[PMID 23932955] Journal of Chemical Neuroanatomy 52: 87-94, Sep 2013.
Stettner, Georg M. Rukhadze, Irma. Mann, Graziella L. Lei, Yanlin. Kubin, Leszek.: Respiratory modulation of lingual muscle activity across sleep-wake states in rats.[PMID 23732510] Respiratory Physiology & Neurobiology 188(3): 308-17, Sep 15 2013.
Duffin, James. Kubin, Leszek. Mateika, Jason H.: Sleep and breathing. Foreword.[PMID 23876742] Respiratory Physiology & Neurobiology 188(3): 231-2, Sep 15 2013.
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.[PMID 22509173] Frontiers in Neurology 3(Article 51): 1-13, 2012.
Volgin, Denys V. Kubin, Leszek.: Reduced sleep and impaired sleep initiation in adult male rats exposed to alcohol during early postnatal period.[PMID 22698707] Behavioural Brain Research 234(1): 38-42, Sep 1 2012.
Fenik, Victor B. Marchenko, Vitaliy. Davies, Richard O. Kubin, Leszek.: Inhibition of A5 Neurons Facilitates the Occurrence of REM Sleep-Like Episodes in Urethane-Anesthetized Rats: A New Role for Noradrenergic A5 Neurons? [PMID 22855683] Frontiers in Neurology [electronic resource]. 3: 119, 2012.
Stettner GM, Fenik VB, Kubin L: Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons.[PMID 22016369] 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.[PMID 21335420] Experimental Physiology 96: 548-555, 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.[PMID 22205596] Archives Italiennes de Biologie 149: 499-515, 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.[PMID 21420437] Behavioural Brain Research 221: 324-328, 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.[PMID 22015761] Neuroscience Letters 505: 176-179, 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.[PMID 20622040] 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.[PMID 19539786] Respiratory Physiology & Neurobiology 167: 307-315, 2009.
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Last updated: 11/16/2021
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