Role of Astrocytes in Central Respiratory Control

Astrocytes, once regarded primarily as structural and metabolic support cells, are now increasingly recognized as active participants in neural information processing. Within respiratory control networks, astrocytes are widely distributed throughout the brainstem and spinal cord, where they engage in bidirectional communication with neurons to regulate breathing. This review summarizes current knowledge regarding the roles of astrocytes in respiratory rhythm and pattern generation, central respiratory chemoreception, hypoxic ventilatory responses, respiratory plasticity, and respiratory pathophysiology. Recent advancements in calcium imaging, optogenetics, and pharmacology have revealed that astrocytes modulate respiratory network activity through intracellular Ca²⁺ signaling and the release of gliotransmitters, particularly ATP. In the ventrolateral medulla and the parafacial respiratory group/retrotrapezoid nucleus, astrocytes contribute to central CO₂/H⁺ chemoreception through mechanisms involving connexin hemichannels, potassium channels, and purinergic signaling. Emerging evidence further suggests that astrocytes participate in central hypoxic responses and adaptive respiratory plasticity. In addition, astrocytic dysfunction has been implicated in several disorders affecting respiratory control, including brainstem astrocytoma, Rett syndrome, sudden infant death syndrome, and sudden unexpected death in epilepsy. Collectively, accumulating evidence identifies astrocytes as integral components of respiratory control networks that contribute to both the maintenance of respiratory homeostasis and the pathogenesis of respiratory dysfunction. A deeper understanding of astrocyte-neuron interactions may provide novel therapeutic opportunities for the treatment of respiratory disorders.