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Dr Alexander Gourine

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Name: Alexander Gourine Email: a.gourine@ucl.ac.uk
Title: Dr Tel: 020 7679 4384
Department: Neuroscience, Physiology & Pharmacology Fax:
Position: Senior Research Fellow/ Reader Address: Physiology, Medical Sciences Building, UCL South Cloisters, Gower St, London, WC1E 6BT
Research Domain: Experimental Medicine, Neuroscience Web Page: Personal Web Page

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Research Description

Chemosensory control of breathing

We breathe continuously from birth until death to maintain appropriate concentrations of oxygen, CO2 and hydrogen ions (H+) in the blood in various environmental and physiological conditions. Respiratory sensors located in the brain monitor changes in the blood levels of CO2 and H+ and evoke adaptive changes in breathing appropriate to the current metabolic rate and activity. The identity of these respiratory CO2 sensors as yet remains to be determined. The specific molecular mechanisms which transduce changes in blood concentrations of CO2 and H+ into a modified pattern of breathing are also remain elusive. We use a combination of experimental models ranging from cell culture to in vivo animal preparations to identify the nature of the respiratory sensors in the brain and pinpoint the mechanisms which underlie their sensitivity to changes in the levels of CO2 and H+ in the blood.

Research supported by the Wellcome Trust.

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Autonomic control in pathological conditions

Beat-by-beat activity of the heart and every single breath are controlled by the central nervous system. Brain mechanisms responsible for regulation of the activity of the cardiovascular and respiratory systems exhibit significant plasticity which ensures survival and adaptation of the organism in changeable environment. In pathological conditions this plasticity may result in adaptive and beneficial modifications in central cardiorespiratory control, but may also lead to maladaptive and detrimental changes when disease is progressing. Surprisingly, very little is known about the mechanisms underlying changes in the activity of brain centres involved in cardiorespiratory control in pathological conditions. In collaboration with Dr Gareth Ackland we investigate neuronal and molecular mechanisms responsible for modifications in the central nervous mechanisms of cardiovascular and respiratory control in different pathological conditions, including heart failure and systemic inflammation leading to sepsis.

Research supported by The Royal Free Peter Samuel Fund and The Intensive Care Society.


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Research Activities

Autonomic neuroscience

Neural Networks and Sympathetic Motor Control

Education Description

UCL Collaborators

Dr Gareth Ackland; Dr Brian King; Prof Michael Duchen; Prof Michael Spyer; Prof Michael Gilbey

External Collaborators

Publications

    2013

    • Marina N, Tang F, Figueiredo M, Mastitskaya S, Kasimov V, Mohamed-Ali V, Roloff E, Teschemacher AG, Gourine AV, Kasparov S (2013). Purinergic signalling in the rostral ventro-lateral medulla controls sympathetic drive and contributes to the progression of heart failure following myocardial infarction in rats.. Basic Res Cardiol, 108(1), 317 - . doi:10.1007/s00395-012-0317-x
    • Paton JF, Sobotka PA, Fudim M, Engelman ZJ, Hart EC, McBryde FD, Abdala AP, Marina N, Gourine AV, Lobo M, Patel N, Burchell A, Ratcliffe L, Nightingale A (2013). The carotid body as a therapeutic target for the treatment of sympathetically mediated diseases.. Hypertension, 61(1), 5 - 13. doi:10.1161/HYPERTENSIONAHA.111.00064

    2012

    • Mastitskaya S, Marina N, Gourine A, Gilbey MP, Spyer KM, Teschemacher AG, Kasparov S, Trapp S, Ackland GL, Gourine AV (2012). Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones.. Cardiovasc Res, 95(4), 487 - 494. doi:10.1093/cvr/cvs212
    • Plun-Favreau H, Burchell VS, Holmström KM, Yao Z, Deas E, Cain K, Fedele V, Moisoi N, Campanella M, Miguel Martins L, Wood NW, Gourine AV, Abramov AY (2012). HtrA2 deficiency causes mitochondrial uncoupling through the F₁F₀-ATP synthase and consequent ATP depletion.. Cell Death Dis, 3, e335 - . doi:10.1038/cddis.2012.77
    • Basalay M, Barsukevich V, Mastitskaya S, Mrochek A, Pernow J, Sjöquist PO, Ackland GL, Gourine AV, Gourine A (2012). Remote ischaemic pre- and delayed postconditioning - similar degree of cardioprotection but distinct mechanisms.. Exp Physiol, 97(8), 908 - 917. doi:10.1113/expphysiol.2012.064923
    • Abdala AP, McBryde FD, Marina N, Hendy EB, Engelman ZJ, Fudim M, Sobotka PA, Gourine AV, Paton JF (2012). Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat.. J Physiol, 590(Pt 17), 4269 - 4277. doi:10.1113/jphysiol.2012.237800
    • Christie IN, Wells JA, Southern P, Marina N, Kasparov S, Gourine AV, Lythgoe MF (2012). fMRI response to blue light delivery in the naïve brain: Implications for combined optogenetic fMRI studies.. Neuroimage, 66C, 634 - 641. doi:10.1016/j.neuroimage.2012.10.074

    2011

    • Gourine AV, Kasparov S (2011). Astrocytes as brain interoceptors.. Exp Physiol, 96(4), 411 - 416. doi:10.1113/expphysiol.2010.053165
    • Marina N, Abdala AP, Korsak A, Simms AE, Allen AM, Paton JF, Gourine AV (2011). Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata.. Cardiovasc Res, 91(4), 703 - 710. doi:10.1093/cvr/cvr128
    • Figueiredo M, Lane S, Tang F, Liu BH, Hewinson J, Marina N, Kasymov V, Souslova EA, Chudakov DM, Gourine AV, Teschemacher AG, Kasparov S (2011). Optogenetic experimentation on astrocytes.. Exp Physiol, 96(1), 40 - 50. doi:10.1113/expphysiol.2010.052597
    • Trapp S, Tucker SJ, Gourine AV (2011). Respiratory responses to hypercapnia and hypoxia in mice with genetic ablation of Kir5.1 (Kcnj16).. Exp Physiol, 96(4), 451 - 459. doi:10.1113/expphysiol.2010.055848

    2010

    • Ackland GL, Del Arroyo AG, Yao ST, Stephens RC, Dyson A, Klein NJ, Singer M, Gourine AV (2010). Low molecular weight polyethylene glycol improves survival in experimental sepsis.. Critical Care Medicine, 38, 629 - 636.
    • Ackland GL, Yao ST, Rudiger A, Dyson A, Stidwill R, Poputnikov D, Singer M, Gourine AV (2010). Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats.. Crit Care Med, 38(2), 388 - 394. doi:10.1097/CCM.0b013e3181c03dfa
    • Gourine AV, Kasymov V, Marina N, Tang F, Figueiredo MF, Lane S, Teschemacher AG, Spyer KM, Deisseroth K, Kasparov S (2010). Astrocytes control breathing through pH-dependent release of ATP.. Science, 329(5991), 571 - 575. doi:10.1126/science.1190721
    • Vaarmann A, Gandhi S, Gourine AV, Abramov AY (2010). Novel pathway for an old neurotransmitter: dopamine-induced neuronal calcium signalling via receptor-independent mechanisms.. Cell Calcium, 48(2-3), 176 - 182. doi:10.1016/j.ceca.2010.08.008
    • Marina N, Abdala AP, Trapp S, Li A, Nattie EE, Hewinson J, Smith JC, Paton JF, Gourine AV (2010). Essential role of Phox2b-expressing ventrolateral brainstem neurons in the chemosensory control of inspiration and expiration.. J Neurosci, 30(37), 12466 - 12473. doi:10.1523/JNEUROSCI.3141-10.2010
    • Erlichman JS, Leiter JC, Gourine AV (2010). ATP, glia and central respiratory control. RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 173(3), 305 - 311. doi:10.1016/j.resp.2010.06.009
    • Huckstepp RTR, Bihi RI, Eason R, Spyer KM, Dicke N, Willecke K, Marina N, Gourine AV, Dale N (2010). Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. J PHYSIOL-LONDON, 588(20), 3901 - 3920. doi:10.1113/jphysiol.2010.192088

    2009

    • Tian F, Gourine AV, Huckstepp RT, Dale N (2009). A microelectrode biosensor for real time monitoring of L-glutamate release. Anal.Chim.Acta, 645(1-2), 86 - 91.
    • Paschalis A, Churchill L, Marina N, Kasymov V, Gourine A, Ackland G (2009). beta1-Adrenoceptor distribution in the rat brain: an immunohistochemical study.. Neurosci Lett, 458(2), 84 - 88. doi:10.1016/j.neulet.2009.04.023
    • Spyer KM, Gourine AV (2009). Chemosensory pathways in the brainstem controlling cardiorespiratory activity. PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 364(1529), 2603 - 2610. doi:10.1098/rstb.2009.0082
    • Gourine AV, Wood JD, Burnstock G (2009). Purinergic signalling in autonomic control.. Trends Neurosci, 32(5), 241 - 248. doi:10.1016/j.tins.2009.03.002
    • Gourine AV, Spyer KM (2009). Autonomic Nervous System: Central Respiratory Control. In (Ed.), New Encyclopedia of Neuroscience (pp. 883 - 890). : .

    2008

    • Trapp S, Aller MI, Wisden W, Gourine AV (2008). A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing. J.Neurosci., 28(35), 8844 - 8850.
    • Gourine AV, Dale N, Korsak A, Llaudet E, Tian F, Huckstepp R, Spyer KM (2008). Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary stretch receptor (Breuer-Hering) reflex pathway. J PHYSIOL-LONDON, 586(16), 3963 - 3978. doi:10.1113/jphysiol.2008.154567
    • Gourine A, Bondar SI, Spyer KM, Gourine AV (2008). Beneficial effect of the central nervous system beta-adrenoceptor blockade on the failing heart.. Circulation Research, 102(6), 633 - 636. doi:10.1161/CIRCRESAHA.107.165183
    • Gourine AV, Spyer KM, Gourine A (2008). Beta-blockers: acting in the brain but healing the heart. Expert.Rev.Cardiovasc.Ther., 6(7), 913 - 915.

    2007

    • Gourine VN, Krotov VP, Gourine AV, Korol'kov VI, Gordeev I (2007). [Effects of antiorthostatic hypokinesia on blood levels of interleukine-1beta and interleukine-6 in primates]. Space & Ecological Medicine (in Russian), 41(6), 56 - 58.
    • Ackland GL, Kasymov V, Gourine AV (2007). Physiological and pathophysiological roles of extracellular ATP in chemosensory control of breathing.. Biochem Soc Trans, 35(Pt 5), 1264 - 1268. doi:10.1042/BST0351264
    • Gourine AV, Dale N, Llaudet E, Poputnikov DM, Spyer KM, Gourine VN (2007). Release of ATP in the central nervous system during systemic inflammation: real-time measurement in the hypothalamus of conscious rabbits.. The Journal of Physiology, 585(1), 305 - 316. doi:10.1113/jphysiol.2007.143933

    2006

    • Lapikov SI, Gourine VN, Gourine AV (2006). [Response of the afferent vagal fibers to lipopolysaccharides of gram-negative bacteria administered intrapulmonarily: an experimental model]. Human Physiology (in Russian), 32(1), 108 - 114.
    • Spyer KM, Ackland GL, Gourine AV (2006). Neurophysiology: Overview.. In (Ed.), Encyclopedia of respiratory medicine (pp. 131 - 138). : .

    2005

    • Gourine AV, Llaudet E, Dale N, Spyer KM (2005). Release of ATP in the ventral medulla during hypoxia in rats: Role in hypoxic ventilatory response. J NEUROSCI, 25(5), 1211 - 1218. doi:10.1523/JNEUROSCI.3763-04.2005
    • Gourine AV (2005). Wellcome Prize Lecture. On the peripheral and central chemoreception and control of breathing: an emerging role of ATP. The Journal of Physiology, 568(3), 715 - 724. doi:10.1113/jphysiol.2005.095968
    • Gourine AV, Llaudet E, Dale N, Spyer KM (2005). ATP is a mediator of chemosensory transduction in the central nervous system.. Nature, 436(7047), 108 - 111. doi:10.1038/nature03690
    • Gourine AV, Poputnikov DM, Zhernosek N, Melenchuk EV, Gerstberger R, Spyer KM, Gourine VN (2005). P2 receptor blockade attenuates fever and cytokine responses induced by lipopolysaccharide in rats. BRIT J PHARMACOL, 146(1), 139 - 145. doi:10.1038/sj.bjp.0706287

    2004

    • Gourine AV, Dale N, Gourine VN, Spyer KM (2004). Fever in systemic inflammation: roles of purines.. Frontiers in Bioscience, 9, 1011 - 1022.
    • Gourine AV, Dale N, Spyer KM (2004). Chemosensory control of the respiratory function. Working towards understanding the role of ATP-mediated purinergic signalling.. Advances in Experimental Medicine and Biology, 551, 31 - 38.
    • Spyer KM, Dale N, Gourine AV (2004). ATP is a key mediator of central and peripheral chemosensory transduction.. Experimental Physiology, 89(1), 53 - 59.

    2003

    • Rong W, Gourine AV, Cockayne DA, Xiang Z, Ford APDW, Spyer KM, Burnstock G (2003). Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. Journal of Neuroscience, 23(36), 11315 - 11321.
    • Gourine AV, Spyer KM (2003). Chemosensitivity of medullary respiratory neurones. A role for ionotropic P2X and GABA(A) receptors.. Advances in Experimental Medicine and Biology, 536, 375 - 387.
    • Yao ST, Gourine AV, Spyer KM, Barden JA, Lawrence AJ (2003). Localisation of P2X2 receptor subunit immunoreactivity on nitric oxide synthase expressing neurones in the brain stem and hypothalamus of the rat: a fluorescence immunohistochemical study.. Neuroscience, 121(2), 411 - 419.
    • Gourine AV, Atkinson L, Deuchars J, Spyer KM (2003). Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X2 receptor subunit.. The Journal of Physiology, 552(1), 197 - 211. doi:10.1113/jphysiol.2003.045294

    2002

    • Dale N, Gourine AV, Llaudet E, Bulmer D, Thomas T, Spyer KM (2002). Rapid adenosine release in the nucleus tractus solitarii during defence response in rats: real-time measurement in vivo. The Journal of Physiology, 544.1, 149 - 160.
    • Gourine AV, Melenchuk EV, Poputnikov DM, Gourine VN, Spyer KM (2002). Involvement of purinergic signalling in central mechanisms of body temperature regulation in rats. British Journal of Pharmacology, 135(8), 2047 - 2055.
    • Gourine VN, Gourine AV, Melenchuk EV, Spyer KM (2002). Effect of activation and blockade of central P2X receptors on body temperature. Russian Journal of Physiology, 88(6), 731 - 740.
    • Gourine AV, Llaudet E, Thomas T, Dale N, Spyer KM (2002). Adenosine release in nucleus tractus solitarii does not appear to mediate hypoxia-induced respiratory depression in rats. The Journal of Physiology, 544(1), 161 - 170.
    • Gourine AV, Gourine VN, Tesfaigzi Y, Caluwaerts N, Van Leuven F, Kluger MJ (2002). Role of alpha(2)-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice.. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 283(1), R218 - R226.

    2001

    • Gourine AV, Rudolph K, Korsak AS, Kubatko J, Tesfaigzi J, Kozak W, Kluger MJ (2001). Role of capsaicin-sensitive afferents in fever and cytokine responses during systemic and local inflammation in rats.. Neuroimmunomodulation, 9(1), 13 - 22.
    • Gourine AV, Spyer KM (2001). Chemosensitivity of medullary inspiratory neurones: A role for GABA(A) receptors?. NEUROREPORT, 12(15), 3395 - 3400.

    2000

    • Tzschentke B, Basta D, Gourine AV, Gourine VN (2000). Influence of bombesin on neuronal hypothalamic thermosensitivity during the early postnatal period in the Muscovy duck (Cairina moschata).. Regulatory Peptides, 88(1), 33 - 39. doi:10.1016/S0167-0115(99)00114-7
    • Gourine AV, Rudolph K, Leon LR, Kluger MJ (2000). Effect of interleukin-11 on body temperature in afebrile and febrile rats.. Neuroimmunomodulation, 8(1), 8 - 12.
    • Gourine AV, Leon LR, Rudolph K, Tesfaigzi J, Kluger MJ (2000). Cytokine cascade induced by endotoxin in TNF double receptor knockout mice: Evidence supporting a role for IL-10 in mediating antipyretic action of TNF. Journal of Thermal Biology, 25(1-2), 21 - 27. doi:10.1016/S0306-4565(99)00051-0

    1999

    • Gourine VN, Sandakov DB, Gourine AV (1999). [Brain proteinase activity and the mobilization of endogenous proteolytic inhibitors as factors in the development of the functional state of the body]. Human Physiology (in Russian), 25(1), 71 - 77.
    • Gourine VN, Sandakov DB, Gourine AV (1999). [Role of proteinase inhibitors in the process that provide coupling between body's functional systems]. Vestn.Ross.Akad.Med.Nauk (in Russian), (6), 25 - 29.

    1998

    • Gourine AV, Rudolph K, Tesfaigzi J, Kluger MJ (1998). Role of hypothalamic interleukin-1beta in fever induced by cecal ligation and puncture in rats.. American Journal of Physiology, 275(3), R754 - R761.
    • Rudolph K, Gourine AV, Korsak AS, Kluger MJ (1998). Interleukin-6 and tumor necrosis factor-alpha during fever induced by bacterial infection.. Annals of the New York Academy of Sciences, 856, 300 - 303.
    • Gourine AV, Leon LR, Rudolph K, Korsak AS, Kluger MJ (1998). Anterior hypothalamic interleukin-1 receptors are involved in mediation of fever during bacterial sepsis in rats.. Annals of the New York Academy of Sciences, 856, 266 - 269.
    • Semenenia IN, Gourine AV (1998). [Changes in the prolactin content of the cerebrospinal fluid and blood serum in rabbits in dynamic hyperthermia induced by Freund's complete adjuvant]. Zh.Evol.Biokhim.Fiziol. (in Russian), 34(2), 270 - 272.

    1997

    • Gourine VN, Gourine AV (1997). [Role of the processes of disinhibition of pacemakers in reflex activity of neural centers]. Human Physiology (in Russian), 23(2), 147 - 149.
    • Gourine AV (1997). [The functional role of nitric oxide in the central nervous system]. Adv Physiol Sci (in Russian), 28(1), 53 - 60.

    1995

    • Semenenia IN, Gourine AV (1995). [The neurotropic effects developing on the administration of Freund's complete adjuvant (FCA) to rats]. Zh.Vyssh.Nerv.Deiat.Im I.P.Pavlova (in Russian), 45(4), 817 - 818.
    • Gourine AV (1995). Pharmacological evidence that nitric oxide can act as an endogenous antipyretic factor in endotoxin-induced fever in rabbits.. General Pharmacology, 26(4), 835 - 841. doi:10.1016/0306-3623(94)00240-N

    1994

    • Koulchitsky SV, Azev OA, Gourine AV, Kulchitsky VA (1994). Capsaicin-sensitive area in the ventral surface of the rat medulla.. Neuroscience Letters, 182(2), 129 - 132. doi:10.1016/0304-3940(94)90780-3