The interaction between retrotrapezoid nucleus astrocytes and neurons on respiratory responses promoted by central chemoreflex activation

• Grant number: 11/13462-7
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2011
• Effective date (End): November 30, 2015
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Cleyton Roberto Sobrinho
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 13/02350-9 - Regulation of ventral surface CO2/H+-sensitive neurons by purinergic signalling in newborn rats, BE.EP.DR

Abstract

The retrotrapezoid nucleus (RTN), which is located ventrally to the facial motor nucleus, very close to the ventrolateral medulla surface, represents the main cluster of cells with chemosensitive characteristics. These neurons are highly sensitive even to an increased CO2 partial pressure or a reduction in pH. In these conditions, the RTN neurons leading to an increased respiratory activity, restoring blood gas homeostasis. However, the mechanisms by which these neurons detect these changes are not entirely clear, and in this sense, a series of studies have attributed part of chemosensitivity in the region of RTN. The glial cells (astrocytes), which would promote the release of neurotransmitters such as ATP, would also lead the activation of neurons and consequently increasing the respiratory activity. Therefore, the aim of this project is to elucidate the possible interaction between astrocytes and neurons of the RTN in the respiratory responses evoked by activation of central chemoreceptors. Thus, the protocols proposed in this project will evaluate: 1) the activation pattern of astrocytes by the analysis of Fos protein expression in awake animals subjected to hypercapnia, 2) the pattern of respiratory activity promoted by astrocytes after local administration of the RTN fluorocitrato gliotoxin and 3) the role of purinergic signaling in this context inserted through the local application of the RTN purinergic receptor antagonists.

Scientific publications

(5)

(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)

SOBRINHO, CLEYTON R.; GONCALVES, CHRISTOPHER M.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. Fluorocitrate-mediated depolarization of astrocytes in the retrotrapezoid nucleus stimulates breathing. Journal of Neurophysiology, v. 118, n. 3, p. 1690-1697, SEP 2017. Web of Science Citations: 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, MAR 1 2015. Web of Science Citations: 6.

SOBRINHO, CLEYTON R.; WENKER, IAN C.; POSS, ERIN M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. Purinergic signalling contributes to chemoreception in the retrotrapezoid nucleus but not the nucleus of the solitary tract or medullary raphe. JOURNAL OF PHYSIOLOGY-LONDON, v. 592, n. 6, p. 1309-1323, MAR 15 2014. Web of Science Citations: 18.

WENKER, IAN C.; SOBRINHO, CLEYTON R.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. P2Y1 Receptors Expressed by C1 Neurons Determine Peripheral Chemoreceptor Modulation of Breathing, Sympathetic Activity, and Blood Pressure. Hypertension, v. 62, n. 2, p. 263-273, AUG 2013. Web of Science Citations: 19.

WENKER, IAN C.; SOBRINHO, CLEYTON R.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. Regulation of ventral surface CO2/H+-sensitive neurons by purinergic signalling. JOURNAL OF PHYSIOLOGY-LONDON, v. 590, n. 9, p. 2137-2150, MAY 2012. Web of Science Citations: 52.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOBRINHO, Cleyton Roberto. Purinergic mechanism in rostroventrolateral medulla modulate cardiovascular and respiratory responses promoted by central and peripheral chemoreceptors activation.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas São Paulo.