Respiratory stress drives microglial remodeling in the parafacial region of mice

The respiratory parafacial region (pFRG) plays a critical role in chemoreception and ventilatory control, yet the contribution of microglia signaling to respiratory modulation under hypoxic and hypercapnic conditions remains unclear. Here, we examined whether acute changes in blood gases affect respiratory output and microglial morphology within the pFRG of conscious mice. Exposure to acute hypercapnia (7% CO₂) increased ventilation (V_E) in both male and female mice through elevations in respiratory frequency (f_R) and tidal volume (V_T). In contrast, hypoxia (8% O₂) produced a biphasic response: an initial increase in V_E during the first 5-10 min, followed by a subsequent ventilatory depression, primarily driven by a reduction in V_T. Morphological analysis of Iba1⁺ microglia revealed that both hypercapnia and hypoxia significantly increased the total number of microglia and enhanced branching complexity and endpoint counts in the pFRG, whereas cell density remained unchanged. These structural changes were similar between sexes. Together, these findings indicate that microglia within the respiratory parafacial region are dynamically responsive to acute chemosensory challenges. The results show that microglia undergo morphological changes following hypercapnic or hypoxic stimulation, suggesting a potential interaction between microglial activity and respiratory circuit function. Nevertheless, whether these changes directly modulate respiratory networks remains to be determined.