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Neural mechanisms involved on chemoreception

Grant number: 09/54888-7
Support type:Research Projects - Thematic Grants
Duration: November 01, 2011 - October 31, 2015
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Eduardo Colombari
Grantee:Eduardo Colombari
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Co-Principal Investigators:Thiago dos Santos Moreira
Associated grant(s):15/14571-5 - 45th Annual Meeting of the society for neuroscience - neuroscience 2015, AR.EXT
Associated scholarship(s):14/06976-2 - Involvement of serotoninergic mechanisms of the retrotrapezoid nucleus in the sympathetic and respiratory changes induced by intermitente hypoxia, BP.DR
13/22526-4 - Cholinergic function of commissural nucleus of the solitary tract on cardiorespiratory responses to hypoxia, hypercapnia and pH decrease, BP.DR

Abstract

Respiration is a physiological process essential to life. The neural circuit that generates the respiratory rhythm and produces the orderly activation of the various respiratory motor outflows (henceforth called central pattern generator, CPG) it is organized at the braistem level. Brain CO2 is almost certainly detected via changes in pH but how pH is detected, where pH is detected and how brain acidification stimulates breathing (the central chemoreflex) are still controversial. A relatively recent theory postulates that central respiratory chemoreception results from the cumulative effect of pH on the CPG itself and many of its tonic drives. The strongest evidence in favor of the specialized chemoreceptor theory came recently from the most ancient approach to neuroscience, namely human pathophysiology. The congenital central hypoventilation syndrome (CCHS), a rare developmental disease caused by mutations of the transcription factor Phox2b is characterized by a virtually complete loss of the central respiratory chemoreception, typically complete sleep apnea but usually maintained breathing during waking and exercise. At this moment, we don't know the real participation of the Phox2b neurons of the RTN in the control of breathing in an animal model without anesthesia. However, in this thematic project our main objective is to understand the cardio-respiratory responses elicted by hypercapnia in conscious rats with specific lesion of the Phox2b neurons in the RTN. To study the cardio-respiratory effects of hypercapnia we will use different experimental methods, which includes pharmacological, eletrophysiological and imunohistochemistry approaches. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Study confirms how the body regulates high levels of CO2 in the blood 

Scientific publications (20)
(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)
ZOCCAL, DANIEL B.; SILVA, JOSIANE N.; BARNETT, WILLIAM H.; LEMES, EDUARDO V.; FALQUETTO, BARBARA; COLOMBARI, EDUARDO; MOLKOV, YAROSLAV I.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Interaction between the retrotrapezoid nucleus and the parafacial respiratory group to regulate active expiration and sympathetic activity in rats. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 315, n. 5, p. L891-L909, NOV 2018. Web of Science Citations: 3.
FURUYA, WERNER I.; COLOMBARI, EDUARDO; FERGUSON, ALASTAIR V.; COLOMBARI, DEBORA S. A. Effects of acetylcholine and cholinergic antagonists on the activity of nucleus of the solitary tract neurons. Brain Research, v. 1659, p. 136-141, MAR 15 2017. Web of Science Citations: 3.
LEMES, EDUARDO V.; COLOMBARI, EDUARDO; ZOCCAL, DANIEL B. Generation of active expiration by serotoninergic mechanisms of the ventral medulla of rats. Journal of Applied Physiology, v. 121, n. 5, p. 1135-1144, NOV 1 2016. Web of Science Citations: 6.
MOREIRA, THIAGO S.; TAKAKURA, ANA C.; CZEISLER, CATHERINE; OTERO, JOSE J. Respiratory and autonomic dysfunction in congenital central hypoventilation syndrome. Journal of Neurophysiology, v. 116, n. 2, p. 742-752, AUG 2016. Web of Science Citations: 9.
SILVA, JOSIANE N.; LUCENA, ELVIS V.; SILVA, TALITA M.; DAMASCENO, ROSELIA S.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. INHIBITION OF THE PONTINE KOLLIKER-FUSE NUCLEUS REDUCES GENIOGLOSSAL ACTIVITY ELICITED BY STIMULATION OF THE RETROTRAPEZOID CHEMORECEPTOR NEURONS. Neuroscience, v. 328, p. 9-21, JUL 22 2016. Web of Science Citations: 8.
LEMES, E. V.; AIKO, S.; ORBEM, C. B.; FORMENTIN, C.; BASSI, M.; COLOMBARI, E.; ZOCCAL, D. B. Long-term facilitation of expiratory and sympathetic activities following acute intermittent hypoxia in rats. ACTA PHYSIOLOGICA, v. 217, n. 3, p. 254-266, JUL 2016. Web of Science Citations: 10.
BARNA, B. F.; TAKAKURA, A. C.; MULKEY, D. K.; MOREIRA, T. S. Purinergic receptor blockade in the retrotrapezoid nucleus attenuates the respiratory chemoreflexes in awake rats. ACTA PHYSIOLOGICA, v. 217, n. 1, p. 80-93, MAY 2016. Web of Science Citations: 12.
SOBRINHO, CLEYTON R.; KUO, FU-SHAN; BARNA, BARBARA F.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. Cholinergic control of ventral surface chemoreceptors involves Gq/inositol 1,4,5-trisphosphate-mediated inhibition of KCNQ channels. JOURNAL OF PHYSIOLOGY-LONDON, v. 594, n. 2, p. 407-419, JAN 15 2016. Web of Science Citations: 7.
ALVES, THALES B.; TOTOLA, LEONARDO T.; TAKAKURA, ANA C.; COLOMBARI, EDUARDO; MOREIRA, THIAGO S. GABA mechanisms of the nucleus of the solitary tract regulates the cardiovascular and sympathetic effects of moxonidine. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 194, p. 1-7, JAN 2016. Web of Science Citations: 2.
DE BRITO ALVES, JOSE L.; NOGUEIRA, VIVIANE O.; CAVALCANTI NETO, MARINALDO P.; LEOPOLDINO, ANDREIA M.; CURTI, CARLOS; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; WANDERLEY, ALMIR G.; LEANDRO, CAROL G.; ZOCCAL, DANIEL B.; COSTA-SILVA, JOAO H. Maternal Protein Restriction Increases Respiratory and Sympathetic Activities and Sensitizes Peripheral Chemoreflex in Male Rat Offspring. Journal of Nutrition, v. 145, n. 5, p. 907-914, MAY 2015. Web of Science Citations: 21.
BASSI, M.; NAKAMURA, N. B.; FURUYA, W. I.; COLOMBARI, D. S. A.; MENANI, J. V.; DO CARMO, J. M.; DA SILVA, A. A.; HALL, J. E.; COLOMBARI, E. Activation of the brain melanocortin system is required for leptin-induced modulation of chemorespiratory function. ACTA PHYSIOLOGICA, v. 213, n. 4, p. 893-901, APR 2015. Web of Science Citations: 16.
BASSI, M.; FURUYA, W. I.; ZOCCAL, D. B.; MENANI, J. V.; COLOMBARI, E.; HALL, J. E.; DA SILVA, A. A.; DO CARMO, J. M.; COLOMBARI, D. S. A. Control of respiratory and cardiovascular functions by leptin. Life Sciences, v. 125, p. 25-31, MAR 15 2015. Web of Science Citations: 15.
MOREIRA, THIAGO S.; WENKER, IAN C.; SOBRINHO, CLEYTON R.; BARNA, BARBARA F.; TAKAKURA, ANA C.; MULKEY, DANIEL K. Independent purinergic mechanisms of central and peripheral chemoreception in the rostral ventrolateral medulla. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 5, p. 1067-1074, MAR 1 2015. Web of Science Citations: 6.
MULKEY, DANIEL K.; HAWKINS, VIRGINIA E.; HAWRYLUK, JOANNA M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; TZINGOUNIS, ANASTASIOS V. Molecular underpinnings of ventral surface chemoreceptor function: focus on KCNQ channels. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 5, p. 1075-1081, MAR 1 2015. Web of Science Citations: 7.
HAWKINS, VIRGINIA E.; HAWRVLUK, JOANNA M.; TAKAKURA, ANA C.; TZINGOUNIS, ANASTASIOS V.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. HCN channels contribute to serotonergic modulation of ventral surface chemosensitive neurons and respiratory activity. Journal of Neurophysiology, v. 113, n. 4, p. 1195-1205, FEB 15 2015. Web of Science Citations: 21.
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. Web of Science Citations: 9.
ZOCCAL, DANIEL B.; FURUYA, WERNER I.; BASSI, MIRIAN; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO. The nucleus of the solitary tract and the coordination of respiratory and sympathetic activities. FRONTIERS IN PHYSIOLOGY, v. 5, JUN 25 2014. Web of Science Citations: 43.
FURUYA, WERNER I.; BASSI, MIRIAN; MENANI, JOSE V.; COLOMBARI, EDUARDO; ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A. Differential modulation of sympathetic and respiratory activities by cholinergic mechanisms in the nucleus of the solitary tract in rats. Experimental Physiology, v. 99, n. 5, p. 743-758, MAY 1 2014. Web of Science Citations: 8.
TOTOLA, L. T.; ALVES, T. B.; TAKAKURA, A. C.; FERREIRA-NETO, H. C.; ANTUNES, V. R.; MENANI, J. V.; COLOMBARI, E.; MOREIRA, T. S. COMMISSURAL NUCLEUS OF THE SOLITARY TRACT REGULATES THE ANTIHYPERTENSIVE EFFECTS ELICITED BY MOXONIDINE. Neuroscience, v. 250, p. 80-91, OCT 10 2013. Web of Science Citations: 12.
TAKAKURA, ANA C.; MOREIRA, THIAGO S.; DE PAULA, PATRICIA M.; MENANI, JOSE V.; COLOMBARI, EDUARDO. Control of breathing and blood pressure by parafacial neurons in conscious rats. Experimental Physiology, v. 98, n. 1, p. 304-315, JAN 2013. Web of Science Citations: 13.

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