Mechanisms of oxytocin action in astrocytes of the parafacial respiratory group and its influence on the control of respiratory activity

• Grant number: 25/20961-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2026
• End date: January 31, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Milede Hanner Saraiva Paes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/05299-0 - Control of the respiratory rhythm and chemosensitivity by the brainstem: role of molecular, cellular and physiopathology aspects, AP.TEM

Abstract

The parafacial respiratory group/retrotrapezoid nucleus (RTN/pFRG), located in the brainstem, plays a fundamental role in the control of breathing, particularly in modulating the ventilatory response to CO2. Multiple lines of evidence indicate that astrocytes in this region are sensitive to increases in the partial pressure of CO2 (pCO2) and contribute to central chemoreception through the release of ATP, which acts on adjacent chemosensitive neurons. Recent studies suggest that oxytocin (Oxt), a neuropeptide widely distributed throughout the central nervous system, may influence respiratory parameters by acting on specific receptors expressed in astrocytes, such as the oxytocin receptor (OxtR). However, it remains unclear whether activation of these receptors in RTN/pFRG astrocytes can directly modulate the ventilatory response to elevated CO2 levels. Given this, the present project aims to investigate the role of oxytocinergic signaling in astrocytes located in the RTN/pFRG in the modulation of ventilation, both under baseline conditions and during respiratory challenges. To this end, four mouse strains will be used: C57BL/6J, OxtRcre/+, Aldh1l1-Cre/ERT2 BAC, and Ai14, which will be crossbred to generate animals with specific expression of the oxytocin receptor and a fluorescent marker in astrocytes. The animals will undergo stereotaxic viral vector injections targeting the RTN/pFRG region and will subsequently be evaluated by whole-body plethysmography. Histological analyses, including immunofluorescence and in situ hybridization, will also be performed to characterize the target cell populations. We hypothesize that activation of oxytocin receptors in RTN/pFRG astrocytes promotes ATP release, thereby enhancing ventilation in response to CO2. (AU)