Neural mechanisms involved in the diurnal variation of the central chemoreflex control

• Grant number: 13/04216-8
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: May 01, 2014
• End date: February 28, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Mirela Barros Dias
• Grantee: Mirela Barros Dias
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Luciane Helena Gargaglioni Batalhão
• Associated scholarship(s): 18/01781-0 - The role of melanin concentrator hormone (MCH) in the lateral hypothalamus/perifornical area (LH/PFA) and locus coeruleus (LC) in the ventilatory response to hypercapnia in rats during wakefulness and sleep, BP.MS; 17/02181-3 - Role of adenosine and A1 receptors in the lateral hypothalamus and perifornical area (LHA / PFA) in daily variations of the hypercapnic ventilatory response, BP.IC; 16/05174-5 - Group II glutamatergic metabotropic receptors role in lateral hypothalamus and perifornicial area (LH/PFA) in daily variations control of ventilatory responses promoted by central chemoreflex activation, BP.IC; + associated scholarships 15/07288-5 - Role of ATP in lateral hypothalamus and perifornical area (LH/PFA) in daily variations of ventilatory responses induced by central chemoreflex, BP.IC; 14/16552-5 - Glutamatergic ionotropic receptors role in lateral hypothalamus and perifornical area (LH/PFA) in daily modulation of ventilatory responses promoted by central chemoreflex activation, BP.IC; 14/17862-8 - Glutamatergic metabotropic receptors role in lateral hypothalamus and perifornicial area (LH/PFA) in daily variations control of ventilatory responses promoted by central chemoreflex activation, BP.IC - associated scholarships

Abstract

The central chemoreceptors, which comprise neurons highly sensitive to CO2/pH changes, are critical to the respiratory regulation of acid-base balance, and as a result have an important role in mantaining homeostasis. Evidence suggests there is a diurnal variation of central chemoreflex, and a series of studies have attributed to orexinergic neurons of lateral hypothalamus and area perifornical (LH/PFA) the role of circadian modulator of the central chemosensitivity, but the mechanisms involved have not been elucidated so far. The main purpose of this project is to investigate important aspects of the neural-chemical mechanisms associated with the central chemoreception in a vigilance- state and diurnal-cycle dependent manner. Our hypothesis is that glutamatergic, purinergic and glial mechanisms in the LH/PFA have a role in the diurnal variation of central chemoreflex. Moreover, other important objective of this project is to evaluate the importance of the interaction between orexinergic neurons and other chemosensitive sites in the diurnal variation of the central chemoreflex control. To this end, we will use pharmacological, immunohistochemical approaches and central microdialysis in unanesthetized rats. Ventilation will be recorded in a whole body plethysmograph, together with EEG and EMG, and we will study the effects of treatments on breathing in air and hypercapnia (7% CO2), during wakefulness and sleep, in both light and dark periods. With the data to be obtained during the development of this project we hope that we will be able to answer several important questions related to the modulation of the central chemosensitivity, which deficiency is associated with numerous pathophysiological conditions including obstructive sleep apnea. (AU)

Scientific publications

(4)

(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)

DA SILVA, ELIANDRA N.; HORTA-JUNIOR, JOSE DE ANCHIETA C.; GARGAGLIONI, LUCIANE H.; DIAS, MIRELA B.. ATP in the lateral hypothalamus/perifornical area enhances the CO2 chemoreflex control of breathing. Experimental Physiology, v. 103, n. 12, p. 1679-1691, DEC 2018. (15/07288-5, 13/04216-8)

CABRAL RODRIGUES, LAISA TAIS; SALATA, BRUNO; HORTA-JUNIOR, JOSE DE ANCHIETA C.; GARGAGLIONI, LUCIANE H.; DIAS, MIRELA BARROS. Adenosine in the lateral hypothalamus/perifornical area does not participate on the CO2 chemoreflex. Respiratory Physiology & Neurobiology, v. 276, MAY 2020. (16/13136-6, 17/02181-3, 13/04216-8)

CABRAL RODRIGUES, LAISA TAIS; DA SILVA, ELIANDRA NUNES; HORTA-JUNIOR, JOSE DE ANCHIETA C.; GARGAGLIONI, LUCIANE H.; DIAS, MIRELA B.. Glutamate metabotropic receptors in the lateral hypothalamus/perifornical area reduce the CO2 chemoreflex. Respiratory Physiology & Neurobiology, v. 260, p. 122-130, FEB 2019. (14/17862-8, 13/04216-8, 16/05174-5)

DA SILVA, ELIANDRA N.; HORTA-JUNIOR, JOSE DE ANCHIETA C.; GARGAGLIONI, LUCIANE H.; DIAS, MIRELA B.. CO2 exposure enhances Fos expression in hypothalamic neurons in rats during the light and dark phases of the diurnal cycle. Brain Structure & Function, v. 227, n. 8, p. 13-pg., 2022-09-15. (13/04216-8, 19/17693-5)