11 Data figures and text NCOMMS-16-21368C.xlsx

Data used in figures and text in the paper NCOMMS-16-21368C entitled:
D-serine released by astrocytes in the brainstem regulates the breathing response to CO2 levels
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
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 increase the
respiratory frequency (fR). Application of D-serine to brainstem slices also
increases fR, which was prevented by NMDAR blockade. Inhibition of D-serine
synthesis, enzymatic degradation of D-serine, or the sodium
fluoroacetate-induced impairment of astrocyte functions decrease the basal fR
and the CO2-induced respiratory response in vivo and in vitro. Our findings
suggest that astrocytic release of D-serine may account for the glutamatergic contribution to central chemoreception.