Possible role of A2 adenosine receptors in the modulation of glutamatergic transmission in the NTS of mice submitted to sustained hypoxia

• Grant number: 21/01767-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2021
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Benedito Honorio Machado
• Grantee: Juliana Reis Souza
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/15957-2 - Astrocytic modulation on brainstem neurons involved with generation and control of sympathetic and respiratory activities in rodents submitted to hypoxia, AP.TEM

Abstract

Hypoxia is characterized by a reduction in the partial pressure of oxygen in arterial blood (PaO2). Under this condition, peripheral chemoreceptors located mainly in the carotid body are stimulated and trigger autonomic, respiratory and behavioral responses in order to restore oxygen levels in arterial blood. Located on the dorsal surface of the brain stem, the nucleus of the solitary tract (NTS) is an integrating center of several sensory systems, including the synaptic processing of the afferents of the chemoreflex. NTS has a high density of tripartite synapses and recent studies suggest that astrocytes play an important role in reducing the excitatory activity of glutamate, especially when this neurotransmitter is released in excess in situations of hypoxia and ischemia. In this context, the increase in the release of adenosine by astrocytes and/or neurons during acute episodes of hypoxia or ischemia seems to contribute to the reduction of glutamate release. However, there is evidence that previous episodes of hypoxia (hypoxic preconditioning) can alter the effects of new situations of tissue hypoxia in NTS, with emphasis on the decrease in the activation of potassium channels sensitive to ATP in the neuron membrane, which can result in increased cellular excitability. Previous studies from our laboratory demonstrated that previous exposure to sustained hypoxia (SH - FiO2 0.1) for 24 hours promotes an increase in glutamatergic transmission in NTS neurons, suggesting a reduction in inhibitory astrocytic modulation on glutamatergic currents. The main aim of this project is to evaluate the role of adenosine released by astrocytes and/or neurons and their A2 subtype receptors on glutamatergic transmission in NTS neurons in mice submitted to SH for 24h. For this purpose, Wild-type C57BL/6 mice and adenosine A2 subtype receptors knockout mice (KO/A2) will be used. (AU)

Scientific publications

(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)

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)

Academic Publications

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

SOUZA, Juliana Reis. Cardiorespiratory profile and electrophysiological characteristics of neurons in the nucleus of tractus solitarius of adenosine A2A receptors knockout mice submitted to sustained hypoxia. 2023. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.