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Ventral surface chemoreceptor neuronal mechanisms

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)

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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, 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, . (09/54888-7, 10/09776-3, 13/00401-5, 10/15692-7, 13/10573-8, 12/16166-2, 12/03568-5)
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, . (12/10337-0, 09/54888-7, 10/09776-3, 14/04866-5, 11/13462-7, 13/10573-8, 13/02350-9)
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, . (12/10337-0, 09/54888-7, 10/09776-3, 13/10573-8)
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, . (13/10573-8, 13/26540-1, 14/22406-1)
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, . (09/54888-7, 10/09776-3, 13/10573-8)
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, . (09/54888-7, 10/09776-3, 13/10573-8)
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, . (09/54888-7, 13/10573-8)
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, . (11/11934-9, 09/54888-7, 14/22406-1, 13/10573-8)
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, . (09/54888-7, 14/22406-1, 13/10573-8)
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, . (13/10573-8, 13/00401-5, 10/09776-3, 14/22406-1)

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