Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in Glycinergic inhibition

Abstract

The glycine transporter subtype 1 (GIyT1) is widely expressed in astroglial cells throughout the mammalian central nervous system and has been implicated in the regulation of N-methyl-D-aspartate (NMDA) receptor activity. Newborn mice deficient in GIyT1 are anatomically normal but show severe motor and respiratory deficits and die during the first postnatal day. In brainstem slices from GIyT1-deficient mice, in vitro respiratory activity is strikingly reduced but normalized by the glycine receptor (GlyR) antagonist strychnine. Conversely, glycine or the GIyT1 inhibitor sarcosine suppress respiratory activity in slices from wild-type mice. Thus, during early postnatal life, GIyT1 is essential for regulating glycine concentrations at inhibitory GlyRs, and GIyT1 deletion generates symptoms found in human glycine encephalopathy.