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

来自 EBSCO

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作者：

S Beltrán-Castillo，MJ Olivares，RA Contreras，G Zú?Iga，I Llona，R Von Bernhardi，JL Eugenín

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摘要：

Central chemoreception is essential for adjusting breathing to physiological demands, and for maintaining CO2and 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 released-serine, an agonist for the glycine-binding site of the NMDAR, in response to elevated CO2levels. We show that systemic and raphe nucleusd-serine administration to awake, unrestrained mice increases the respiratory frequency. Application ofd-serine to brainstem slices also increases respiratory frequency, which was prevented by NMDAR blockade. Inhibition ofd-serine synthesis, enzymatic degradation ofd-serine, or the sodium fluoroacetate-induced impairment of astrocyte functions decrease the basal respiratory frequency and the CO2-induced respiratory response in vivo and in vitro. Our findings suggest that astrocytic release ofd-serine may account for the glutamatergic contribution to central chemoreception. Astrocytes are involved in chemoreception in brainstem areas that regulate breathing rhythm, and astrocytes are known to released-serine. Here the authors show that astrocyte release ofd-serine contributes to CO2sensing and breathing in brainstem slices, and in vivo in awake unrestrained mice.

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DOI：

10.1038/s41467-017-00960-3

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年份：

2017