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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 type:Research Projects - Thematic Grants
Duration: September 01, 2019 - August 31, 2024
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Benedito Honorio Machado
Grantee:Benedito Honorio Machado
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Davi José de Almeida Moraes
Assoc. researchers:Daniela Accorsi Mendonça Eichenberger
Associated grant(s):20/00201-0 - Multi-User Equipment approved in grant 2018/15957-2: Laser Multiphoton System, AP.EMU
Associated scholarship(s):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

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)