Cardiorespiratory profile and electrophysiological characteristics of neurons in the nucleus of tractus solitarius of adenosine A2A receptors knockout mice submitted to sustained hypoxia

Author(s)

Juliana Reis Souza

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2023-02-02

Examining board members

Benedito Honório Machado; Vagner Roberto Antunes; Luciane Helena Gargaglioni Batalhão

• Advisor: Benedito Honório Machado

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 and respiratory responses in order to restore oxygen levels in arterial blood. The Nucleus Tractus Solitarius (NTS) located on the dorsal surface of the brainstem is an integrating center for several sensory systems, including the synaptic processing of chemoreflex afferents. Previous studies from our laboratory demonstrated that exposure of rats to sustained hypoxia (SH - 24h, FiO2 0.1) promotes an increase in glutamatergic transmission in NTS neurons due to a reduction in inhibitory astrocytic modulation on glutamatergic currents. Adenosine is an important neuromodulator of synaptic transmission and hypoxia and ischemia increase its concentration in the extracellular environment. Previous studies indicate the A2A receptors as an important mechanism by which adenosine modulates the neuronal networks present in the NTS. In this context, the present study we evaluated whether adenosine released in the NTS and acting on its A2A subtype receptors are important to changes in NTS synaptic transmission of mice submitted to SH. For this, we used a knockout mouse model for adenosine A2A subtype receptor. The Balb/c strain was used as wild-type (WT) control. At first, we evaluated the cardiovascular and respiratory functions of non-anesthetized and freely-moving A2A adenosine receptor knockout mice previously submitted to SH protocols or maintained under normoxic conditions. The results obtained with the in vivo characterization of cardiovascular and respiratory functions showed that A2A knockout mice present cardiovascular responses to SH and peripheral chemoreceptor activation similar to their WT control. Under normoxic conditions, A2A knockout mice present a significantly higher baseline respiratory frequency in comparison with the control group, suggesting that adenosine A2A receptors are relevant in generating and/or modulating baseline respiratory activity in mice. The results obtained with the electrophysiological recordings of NTS neurons showed that exposure to SH enhances excitatory glutamatergic transmission in the NTS of WT Balb/c mice, which was not observed in A2A knockout mice, suggesting that adenosine A2A receptors play an important role in the enhancement of excitatory neurotransmission in NTS neurons that occurs after exposure to SH. (AU)

• FAPESP's process: 21/01767-0 - Possible role of A2 adenosine receptors in the modulation of glutamatergic transmission in the NTS of mice submitted to sustained hypoxia
• Grantee: Juliana Reis Souza
• Support Opportunities: Scholarships in Brazil - Master