Astrocytic modulation on brainstem neurons involved with generation and control of sympathetic and respiratory activities in rodents submitted to hypoxia

• Grant number: 18/15957-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2019
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Benedito Honorio Machado
• Grantee: Benedito Honorio Machado
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Davi José de Almeida Moraes
• Associated researchers: Daniela Accorsi Mendonça Eichenberger ; Melina Pires da Silva
• Associated research grant(s): 23/04280-0 - 11th IBRO World Congress of Neuroscience - IBRO2023, AR.EXT; 20/00201-0 - Multi-User Equipment approved in grant 2018/15957-2: Laser Multiphoton System, AP.EMU
• Associated scholarship(s): 24/09071-2 - Role of the peripheral chemoreceptors in development and maintenance of arterial hypertension., BP.IC; 24/06385-6 - Involvement of astrocytes/neurons interaction in the brainstem nuclei in autonomic and respiratory changes observed in mice submitted to sustained hypoxia, BP.PD; 23/18269-8 - Simultaneous evaluation of structural and functional changes of astrocytes and neurons in the NTS of mice submitted to sustained hypoxia, BP.PD; + associated scholarships 24/03471-9 - Involvement of astrocytes and adenosine in the brainstem in the generation of sympathetic and respiratory activities of rodents submitted to sustained hypoxia., BP.TT; 23/10362-9 - New technological approaches for the acquisition, storage and processing of image data of intracellular calcium concentration in astrocytes using Multiphoton microscopy, BE.PQ; 22/05237-8 - Simultaneous evaluation of structural and functional changes of astrocytes and neurons in the NTS of mice submitted to sustained hypoxia., BP.PD; 22/05308-2 - Involvement of astrocytes and adenosine in the brainstem in the generation of sympathetic and respiratory activities of rodents submitted to sustained hypoxia., BP.TT; 22/02138-9 - The role of astrocytes of the lateral parafacial region in the central generation of expiratory and sympathetic activities and in the control of cardiovascular function in mice., BP.PD; 21/08833-8 - Possible role of astrocytes in the brainstem regions in the respiratory changes observed in mice submitted to sustained hypoxia, BP.DR; 21/01767-0 - Possible role of A2 adenosine receptors in the modulation of glutamatergic transmission in the NTS of mice submitted to sustained hypoxia, BP.MS; 20/03955-5 - Effects of sustained hypoxia on the electrophysiological properties and purinergic signaling of the carotid chemoreceptors of rats, BP.DD; 19/21328-0 - Participation of astrocytes in the modulation of NTS neurons involved in the processing of cardiovascular and respiratory components of the chemoreflex of rats submitted to maintained hypoxia, BP.DR; 19/21276-0 - Role of astrocytes in inhibitory transmission in the NTS chemoreflex neural pathways of rats exposed hypoxia maintained, BP.DD; 19/21916-0 - Characterization of the cardiovascular and respiratory alterations of mice previously submitted to sustained hypoxia, BP.IC - associated scholarships

Abstract

The main goal of this Thematic Project is to study the astrocytic modulation on the synaptic transmission of neurons integral to sympathetic and respiratory networks at the brainstem level under normoxic as well as in hypoxic conditions. This important and contemporary topic in the literature is associated to the role of astrocytes and their gliotransmitters on the modulation of synaptic transmission in neuronal networks of autonomic and respiratory functions located at the nucleus tractus solitary (NTS) and in the neurons located in the ventral medulla in charge of generation of sympathetic activity (RVLM) and the respiratory rhythm and pattern (Botzinger and pre-Botzinger complexes). Due to technical and methodological challenges to explore the interaction between the components of the tripartite synapse under physiological conditions, we will use the strategy of inhibition or activation of astrocytes by hypoxia protocols in order to reveal the possible and expected modulation of astrocytes on the synaptic transmission in neurons integral to the sympathetic and respiratory networks at the brainstem of rats and mice. We will use simultaneous electrophysiological recordings (patch-clamp) and real time functional images as well as cellular, molecular biology and genetics approaches. Experiments will be performed in rats as well as in mices. The use of genetically modified mices will allow us a better evaluation of the communication in between astrocytes and neurons. All information to be generated by the experiments proposed for this Thematic Project will be really important for a better understanding of the mechanisms underlying the cardiovascular and respiratory changes observed under hypoxic challenges such as obstructive sleep apnea, heart failure, stroke, and chronic pulmonary diseases. (AU)

Scientific publications

(13)

(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)

RODRIGUES, KARLA L.; SOUZA, JULIANA R.; BAZILIO, DARLAN S.; DE OLIVEIRA, MAURO; MORAES, MELINA P. S.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Changes in the autonomic and respiratory patterns in mice submitted to short-term sustained hypoxia. Experimental Physiology, v. 106, n. 3, FEB 2021. (18/15957-2, 19/21916-0)

PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.; ZOCCAL, DANIEL B.; ABDALA, ANA P.; SMITH, JEFFREY C.; ANTUNES, VAGNER R.; MURPHY, DAVID; DUTSCHMANN, MATHIAS; DHINGRA, RISHI R.; et al. Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years. JOURNAL OF PHYSIOLOGY-LONDON, v. 600, n. 9, p. 27-pg., 2022-04-07. (19/19894-8, 18/15957-2, 19/11863-6, 21/06886-7)

SOUZA, JULIANA R.; LIMA-SILVEIRA, LUDMILA; ACCORSI-MENDONCA, DANIELA; MACHADO, BENEDITO H.. Enhancement of the Evoked Excitatory Transmission in the Nucleus Tractus Solitarius Neurons after Sustained Hypoxia in Mice Depends on A_2A Receptors. Neuroscience, v. 536, p. 15-pg., 2023-11-28. (22/05237-8, 18/15957-2, 21/01767-0)

MACHADO, BENEDITO H.. Evidences That Sympathetic Overactivity and Neurogenic Hypertension Correlate with Changes in the Respiratory Pattern in Rodent Models of Experimental Hypoxia. ARTERIAL CHEMORECEPTORS, v. 1427, p. 11-pg., 2023-01-01. (18/15957-2)

PASCOALOTI-LIMA, JULIO C.; MACHADO, BENEDITO H.; ACCORSI-MENDONCA, DANIELA. Sustained Hypoxia Reduces GABAergic Modulation on NTS Neurons Sending Projections to Ventral Medulla of Rats. Neuroscience, v. 457, p. 1-11, MAR 1 2021. (18/15957-2, 19/21276-0)

PASCOALOTI-LIMA, JULIO C.; MACHADO, BENEDITO H.; ACCORSI-MENDONCA, DANIELA. Sustained Hypoxia Reduces GABAergic Modulation on NTS Neurons Sending Projections to Ventral Medulla of Rats (Retracted article. See vol. 493, pg. 120, 2022). Neuroscience, v. 457, p. 11-pg., 2021-01-28. (18/15957-2, 19/21276-0)

BAZILIO, DARLAN S.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Glutamatergic and purinergic transmitters and astrocyte modulation in the synaptic transmission in the NTS of rats exposed to short-term sustained hypoxia. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 327, n. 4, p. 19-pg., 2024-10-05. (18/15957-2, 19/21328-0)

ACCORSI-MENDONCA, DANIELA; LIMA-SILVEIRA, LUDMILA; MACHADO, BENEDITO H.. Modulation by Astrocytes of AMPA Currents in the NTS Neurons of Mice Is Reduced by Short Term-Sustained Hypoxia. PHYSIOLOGY, v. 39, p. 2-pg., 2024-05-01. (22/05237-8, 18/02336-0, 18/15957-2)

SOUZA, JULIANA REIS; MACHADO, BENEDITO HONORIO. Cardiovascular and respiratory profile of adenosine A 2A receptors knockout mice submitted to sustained hypoxia. PHYSIOLOGY, v. 38, p. 2-pg., 2023-05-01. (21/01767-0, 18/15957-2)

BAZILIO, DARLAN S.; RODRIGUES, KARLA L.; MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Distinct cardiovascular and respiratory responses to short-term sustained hypoxia in juvenile Sprague Dawley and Wistar Hannover rats. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 230, JAN 2021. (18/15957-2)

MAGALHAES, KAROLYNE S.; DA SILVA, MELINA P.; MECAWI, ANDRE S.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.. Intrinsic and synaptic mechanisms controlling the expiratory activity of excitatory lateral parafacial neurones of rats. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 21, OCT 2021. (19/24060-9, 18/15957-2, 19/11863-6, 18/07027-5)

DA SILVA, MELINA P.; MAGALHAES, KAROLYNE S.; DE SOUZA, DANIEL P.; MORAES, DAVI J. A.. Chronic intermittent hypoxia increases excitability and synaptic excitation of protrudor and retractor hypoglossal motoneurones. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 6, FEB 2021. (18/15957-2, 19/11863-6, 19/24060-9, 18/07027-5)

SOUZA, JULIANA R.; DE OLIVEIRA, MAURO; MACHADO, BENEDITO H.. Sustained hypoxia in mice increases parasympathetic but not sympathetic tone. CURRENT RESEARCH IN PHYSIOLOGY, v. 5, p. 8-pg., 2022-01-01. (19/21916-0, 18/15957-2)