Changes in the neural networks involved with the generation and control of sympathetic and respiratory activities in different experimental models of hypoxia

• Grant number: 13/06077-5
• Support Opportunities: Research Projects - Thematic Grants
• Duration: April 01, 2014 - August 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Benedito Honorio Machado
• Grantee: Benedito Honorio Machado
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Daniel Breseghello Zoccal ; Daniela Accorsi Mendonça Eichenberger ; Davi José de Almeida Moraes
• Associated grant(s): 18/11356-4 - Participation of glial cells in the central generation of respiratory rhythm and pattern, AV.EXT; 15/05167-6 - International Society of Autonomic Neuroscience 2015, AR.EXT; 14/07771-5 - 1st PanAmerican Congress of Physiological Science, AR.BR
• Associated scholarship(s): 18/04834-7 - Changes in the sympathetic-respiratory coupling after inhibition of glia/astrocytes in the rostral ventrolateral medulla of rats submitted to chronic intermittent hypoxia, BP.TT; 15/06550-8 - Neural mechanisms involved in the generation of arterial hypertension in female rats submitted to chronic intermittent hypoxia, BP.DR; 15/01073-7 - Electrophysiological characterization of expiratory motoneurons in rats submitted to sustained hypoxia, BP.PD; 14/11101-5 - The influence of inflamatory process on the activity of nucleus tractus solitarius neurons in juvenile rats submitted to sustained hypoxia, BP.DD

Abstract

The neural mechanisms underlying the generation and modulation of the sympathetic outflow and the respiratory motor activities are essential for the physiological regulation of the cardiovascular and respiratory functions and consequently for the maintenance of the life. Changes in any aspect of these complex neural mechanisms may affect the cardiovascular and respiratory functions and generating pathophysiological conditions such as hypertension and obstructive sleep apnea. Taking into account that the groups of neurons underlying both sympathetic and respiratory activities are located in the ventral aspect of the medulla, and also that we have strong experimental evidences of the coupling of these activities, the main purpose of this Program Project Grant (Thematic Project) is to evaluate the neurochemical mechanisms involved in the sympathetic-respiratory coupling, especially under challenges conditions such as the chronic intermittent hypoxia or sustained hypoxia. To reach this goal, we will use several contemporary methods and procedures appropriated to help us to answer the several fundamental questions of this Project. In order to challenge the neural pathways of the peripheral chemo reflex and consequently to induce changes in the sympathetic respiratory coupling, we will use different experimental protocols of hypoxia (intermittent or sustained). To explore the complexity of the neural network involved in the generation of sympathetic and respiratory activities we will use several methods of advanced electrophysiology and cellular biology, which we were able to introduce successfully in our laboratory on the past few years, with the financial support by6FAPESP. On the 11 sub-projects to be developed, we will use from awake freely moving rats to neurons in the slices of the brainstem to evaluated very precise ionic currents that may determine the electrophysiological profile of each group of sympathetic and respiratory neurons in normal and in rats submitted to hypoxia. With this integrated approach from whole animal to isolated neurons, not usual in the large majority of laboratories in the world, we are convinced that the obtained results will contribute very much for a better understanding of the neural mechanisms underlying different pathophysiological conditions such as the neurogenic hypertension. (AU)

Scientific publications

(24)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ACCORSI-MENDONCA, DANIELA; ALMADO, CARLOS E. L.; BONAGAMBA, LENI G. H.; CASTANIA, JACI A.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Enhanced Firing in NTS Induced by Short-Term Sustained Hypoxia Is Modulated by Glia-Neuron Interaction. JOURNAL OF NEUROSCIENCE, v. 35, n. 17, p. 6903-6917, APR 29 2015. (13/06077-5)

MORAES, DAVI J. A.; BONAGAMBA, LENI G. H.; DA SILVA, MELINA P.; MECAWI, ANDRE S.; ANTUNES-RODRIGUES, JOSE; MACHADO, BENEDITO H.. Respiratory Network Enhances the Sympathoinhibitory Component of Baroreflex of Rats Submitted to Chronic Intermittent Hypoxia. Hypertension, v. 68, n. 4, p. 1021-1030, OCT 2016. (13/06077-5, 13/10484-5)

MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Electrophysiological properties of laryngeal motoneurones in rats submitted to chronic intermittent hypoxia. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 3, p. 619-634, FEB 1 2015. (13/06077-5, 13/10484-5)

DA SILVA, MELINA P.; MORAES, DAVI JOSE A.; BONAGAMBA, LENI G. H.; MECAWI, ANDRE DE SOUZA; VARANDA, WAMBERTO A.; MACHADO, BENEDITO H.. Hyperexcitability and plasticity induced by sustained hypoxia on rectus abdominis motoneurons. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 7, p. 1935-1956, APR 2019. (13/06077-5, 13/10484-5)

MORAES, DAVI J. A.; MACHADO, BENEDITO H.; PATON, JULIAN F. R.. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 14, p. 3055-3063, JUL 15 2015. (13/06077-5, 13/10484-5)

ACCORSI-MENDONCA, DANIELA; DA SILVA, MELINA P.; SOUZA, GEORGE M. P. R.; LIMA-SILVEIRA, LUDMILA; KARLEN-AMARANTE, MARLUSA; AMORIM, MATEUS R.; ALMADO, CARLOS E. L.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Pacemaking Property of RVLM Presympathetic Neurons. FRONTIERS IN PHYSIOLOGY, v. 7, SEP 22 2016. (13/06077-5)

ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; FLOR, KARINE C.; DA SILVA, MELINA P.; COSTA-SILVA, JOAO H.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.; MURPHY, DAVID; PATON, JULIAN F. R.. Centrally acting adrenomedullin in the long-term potentiation of sympathetic vasoconstrictor activity induced by intermittent hypoxia in rats. Experimental Physiology, v. 104, n. 9, p. 1371-1383, SEP 2019. (13/06077-5, 15/23467-7, 13/10484-5)

BITTENCOURT-SILVA, PALOMA G.; MENEZES, MIGUEL FURTADO; MENDONCA-JUNIOR, BOLIVAL A.; KARLEN-AMARANTE, MARLUSA; ZOCCAL, DANIEL B.. Postnatal intermittent hypoxia enhances phrenic and reduces vagal upper airway motor activities in rats by epigenetic mechanisms. Experimental Physiology, v. 105, n. 1, p. 148-159, JAN 2020. (13/06077-5, 13/17251-6)

MORAES, DAVI J. A.; DA SILVA, MELINA P.; SPILLER, PEDRO F.; MACHADO, BENEDITO H.; PATON, JULIAN F. R.. Purinergic plasticity within petrosal neurons in hypertension. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 315, n. 5, p. R963-R971, NOV 2018. (15/01073-7, 13/06077-5, 16/24869-4, 13/10484-5)

SOUZA, GEORGE M. P. R.; BARNETT, WILLIAM H.; AMORIM, MATEUS R.; LIMA-SILVEIRA, LUDMILA; MORAES, DAVI J. A.; MOLKOV, I, YAROSLAV; MACHADO, BENEDITO H.. Pre- and post-inspiratory neurons change their firing properties in female rats exposed to chronic intermittent hypoxia. Neuroscience, v. 406, p. 467-486, MAY 15 2019. (13/06077-5, 15/06550-8)

SOUZA, GEORGE MIGUEL P. R.; AMORIM, MATEUS R.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Sex differences in the respiratory-sympathetic coupling in rats exposed to chronic intermittent hypoxia. Respiratory Physiology & Neurobiology, v. 256, n. SI, p. 109-118, OCT 2018. (13/06077-5, 15/06550-8)

ACCORSI-MENDONCA, DANIELA; BONAGAMBA, LENI G. H.; MACHADO, BENEDITO H.. Astrocytic modulation of glutamatergic synaptic transmission is reduced in NTS of rats submitted to short-term sustained hypoxia. Journal of Neurophysiology, v. 121, n. 5, p. 1822-1830, MAY 2019. (13/06077-5)

LIMA-SILVEIRA, LUDMILA; ACCORSI-MENDONCA, DANIELA; BONAGAMBA, LENI G. H.; ALMADO, CARLOS EDUARDO L.; DA SILVA, MELINA P.; NEDOBOY, POLINA E.; PILOWSKY, PAUL M.; MACHADO, BENEDITO H.. Enhancement of excitatory transmission in NTS neurons projecting to ventral medulla of rats exposed to sustained hypoxia is blunted by minocycline. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 11, p. 2903-2923, JUN 2019. (13/06077-5, 14/11101-5, 17/13720-2)

DRAGER, LUCIANO F.; POLOTSKY, VSEVOLOD Y.; O'DONNELL, CHRISTOPHER P.; CRAVO, SERGIO L.; LORENZI-FILHO, GERALDO; MACHADO, BENEDITO H.. Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 309, n. 7, p. H1101-H1111, OCT 1 2015. (12/02953-2, 13/06077-5)

PIJACKA, WIOLETTA; MORAES, DAVI J. A.; RATCLIFFE, LAURA E. K.; NIGHTINGALE, ANGUS K.; HART, EMMA C.; DA SILVA, MELINA P.; MACHADO, BENEDITO H.; MCBRYDE, FIONA D.; ABDALA, ANA P.; FORD, ANTHONY P.; et al. Purinergic receptors in the carotid body as a new drug target for controlling hypertension. Nature Medicine, v. 22, n. 10, p. 1151-1159, OCT 2016. (13/06077-5, 13/10484-5)

ZOCCAL, DANIEL B.. Peripheral chemoreceptors and cardiorespiratory coupling: a link to sympatho-excitation. Experimental Physiology, v. 100, n. 2, p. 143-148, FEB 1 2015. (09/54888-7, 13/06077-5)

PERIM, RAPHAEL R.; AMORIM, MATEUS R.; BONAGAMBA, THE LATE LENI G. H.; MACHADO, BENEDITO H.. Previous exposure to chronic intermittent hypoxia blunts the development of one-kidney, one-clip hypertension in rats. Experimental Physiology, v. 103, n. 4, p. 473-482, APR 1 2018. (13/06077-5)

BAZILIO, DARLAN S.; BONAGAMBA, LENI G. H.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Cardiovascular and respiratory profiles during the sleep-wake cycle of rats previously submitted to chronic intermittent hypoxia. Experimental Physiology, v. 104, n. 9, p. 1408-1419, SEP 2019. (13/06077-5)

MAGALHAES, KAROLYNE S.; SPILLER, PEDRO F.; DA SILVA, MELINA P.; KUNTZE, LUCIANA B.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.. Locus Coeruleus as a vigilance centre for active inspiration and expiration in rats. SCIENTIFIC REPORTS, v. 8, OCT 23 2018. (13/10484-5, 15/01073-7, 17/09071-9, 16/24869-4, 13/06077-5)

MORAES, DAVI J. A.; BONAGAMBA, LENI G. H.; DA SILVA, MELINA P.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.. Role of ventral medullary catecholaminergic neurons for respiratory modulation of sympathetic outflow in rats. SCIENTIFIC REPORTS, v. 7, DEC 4 2017. (13/06077-5, 15/01073-7, 13/10484-5)

AMORIM, MATEUS R.; PENA, RODRIGO F. O.; SOUZA, GEORGE M. P. R.; BONAGAMBA, LENI G. H.; ROQUE, ANTONIO C.; MACHADO, BENEDITO H.. Firing properties of ventral medullary respiratory neurons in sino-aortic denervated rats. Experimental Physiology, v. 104, n. 1, p. 39-49, JAN 2019. (13/06077-5, 15/50122-0, 13/15195-1, 13/07699-0, 13/25667-8)

AMORIM, MATEUS R.; BONAGAMBA, LENI G. H.; SOUZA, GEORGE M. P. R.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Changes in the inspiratory pattern contribute to modulate the sympathetic activity in sino-aortic denervated rats. Experimental Physiology, v. 102, n. 9, p. 1100-1117, SEP 1 2017. (13/06077-5, 13/15195-1)

TAXINI, CAMILA L.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.; BICEGO, KENIA C.; GARGAGLIONI, LUCIANE H.; ZOCCAL, DANIEL B.. ROLE OF A5 NORADRENERGIC NEURONS IN THE CHEMOREFLEX CONTROL OF RESPIRATORY AND SYMPATHETIC ACTIVITIES IN UNANESTHETIZED CONDITIONS. Neuroscience, v. 354, p. 146-157, JUN 23 2017. (13/06077-5, 13/17251-6)

AMORIM, MATEUS R.; SOUZA, GEORGE MIGUEL P. R.; MACHADO, BENEDITO H.. Possible Breathing Influences on the Control of Arterial Pressure After Sino-aortic Denervation in Rats. CURRENT HYPERTENSION REPORTS, v. 20, n. 1, JAN 2018. (13/06077-5, 13/15195-1)