D-serine released by astrocytes in brainstem regulates breathing response to CO₂ levels.

ABSTRACT: Central chemoreception is essential for adjusting breathing to physiological demands, and for maintaining CO₂ and pH homeostasis in the brain. CO₂-induced ATP release from brainstem astrocytes stimulates breathing. NMDA receptor (NMDAR) antagonism reduces the CO₂-induced hyperventilation by unknown mechanisms. Here we show that astrocytes in the mouse caudal medullary brainstem can synthesize, store, and release D-serine, an agonist for the glycine-binding site of the NMDAR, in response to elevated CO₂ levels. We show that systemic and raphe nucleus D-serine administration to awake, unrestrained mice increases the respiratory frequency. Application of D-serine to brainstem slices also increases respiratory frequency, which was prevented by NMDAR

SUBMITTER: Beltran-Castillo S 

PROVIDER: S-EPMC5635109 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature