An astrocyte toxin influences the pattern of breathing and the ventilatory response to hypercapnia in neonatal rats

Recent in vitro data suggest that astrocytes may modulate respiration. To examine this question in vivo, we treated 5-day-old rat pups with methionine sulfoximine (MS), a compound that alters carbohydrate and glutamate metabolism in astrocytes, but not neurons. MS-treated pups displayed a reduced breathing frequency (f) in baseline conditions relative to saline-treated pups. Hypercapnia (5% CO2) increased f in both groups, but f still remained significantly lower in the MS-treated group. No differences between treatment groups in the responses to hypoxia (8% O-2) were observed. Also, MS-treated rats showed an enhanced accumulation of glycogen in neurons of the facial nucleus, the nucleus ambiguus, and the hypoglossal nucleus, structures that regulate respiratory activity and airway patency. An altered transfer of nutrient molecules from astrocytes to neurons may underlie these effects of MS, although direct effects of MS upon neurons or upon peripheral structures that regulate respiration cannot be completely ruled out as an explanation. (c) 2005 Elsevier B.V. All rights reserved.