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Ventral surface chemoreceptor neuronal mechanisms

Grant number: 13/10573-8
Support type:Regular Research Grants
Duration: June 01, 2014 - May 31, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Thiago dos Santos Moreira
Grantee:Thiago dos Santos Moreira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Breathing is essential for the homeostasis of the organism , which promotes the setting of the O2 and CO2 levels in the blood and tissues. It is well established that the central and peripheral chemoreceptors detect changes in the concentration of arterial blood gases and transmit this information to cardiorespiratory centers that regulate breathing and sympathetic activity to generate adequate ventilation perfusion to tissues. The deficiency in chemoreceptor activity is associated with numerous problems including sleep apnea, sudden infant death syndrome, a congenital central hypoventilation syndrome and hypertension. However, the cellular and molecular mechanisms of central chemoreception remains to be elucidated, as well as neural integration between the central and peripheral reflexes. Many regions are important in chemoreception , including the nucleus of the solitary tract (NTS), raphe (RPa) and retrotrapezoid nucleus (RTN). Within the RTN region, the central chemoreception mechanism appears to involve the activation of chemosensitive neurons, which detect changes CO2/pH, possibly being modulated by purinergic signaling. However, the mechanisms by which these neurons detect these changes are not fully understood, and in this sense, a number of studies have attributed part of chemosensitivity in the RTN region, glial cells (astrocytes), which would promote the release of neurotransmitters such as ATP, leading to activation of neurons and consequently to increased respiratory activity. Thus , the main objective of this project is to try to identify the involvement of purinergic signaling in regions crucial for cardiorespiratory control (NTS, RTN and RPa) and possible involvement in the activation of the central chemoreflex . Additionally we will also evaluate the possible interaction between astrocytes and neurons in the NTS , RTN and RPa, as well as the selective activation of astrocytes using the optogenetics tecnhique. The experiments outlined in this project seek to test these hypotheses and will be performed by using electrophysiological and anatomical techniques. (AU)

Scientific publications (10)
(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)
SILVA, TALITA M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Acute hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the C1 region. Experimental Neurology, v. 285, n. A, p. 1-11, NOV 2016. Web of Science Citations: 8.
OLIVEIRA, LUIZ M.; MOREIRA, THIAGO S.; KUO, FU-SHAN; MULKEY, DANIEL K.; TAKAKURA, ANA C. alpha(1)- and alpha(2)-adrenergic receptors in the retrotrapezoid nucleus differentially regulate breathing in anesthetized adult rats. Journal of Neurophysiology, v. 116, n. 3, p. 1036-1048, SEP 2016. Web of Science Citations: 10.
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.
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: 5.
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.
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.

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