Increased Fos immunoreactivity in astrocytes in the raphe pallidus under hypoxia, not hypercapnia

The raphe pallidus (RPa), a part of the caudal medullary raphe nucleus, has been suggested to participate in respiratory regulation. Therefore, hypoxia and hypercapnia are expected to affect the expression of Fos, a marker of cellular activation, in the RPa; however, there is currently no consensus on Fos expression in the RPa under hypoxic and hypercapnic conditions. The present study investigated the distribution of Fos expression in the RPa of rats exposed to hypoxia (10% O₂), hypercapnia (8% CO₂), and hypercapnic hypoxia (10% O₂ and 8% CO₂) for 2 h. To confirm whether activation of the RPa affects respiratory function, an electrical stimulation was applied to the RPa of anesthetized rats. The stimulation induced a significant increase in the respiratory rate, which was similar to the respiratory changes induced by hypoxia. An immunohistochemical analysis revealed two types of cells in the RPa: serotonin-immunoreactive neurons and SOX9-immunoreactive astrocytes. Hypoxia significantly increased Fos immunoreactivity in astrocytes in the rostral region of the RPa, but did not affect Fos immunoreactivity in serotonergic neurons. In contrast, hypercapnia and hypercapnic hypoxia did not affect Fos immunoreactivity in either cell type in any region. These results suggest that astrocytes in the RPa are specifically activated by hypoxia and actively contribute to the respiratory response to hypoxia.