title: Glial glycine transporter 1 function is essential for early postnatal survival but dispensable in adult mice.
abstract: The glycine transporter 1 (GlyT1) is expressed in astrocytes and selected neurons of the mammalian CNS. In newborn mice, GlyT1 is crucial for efficient termination of glycine-mediated inhibitory neurotransmission. Furthermore, GlyT1 has been implicated in the regulation of excitatory N-methyl-D-asparate (NMDA) receptors. To evaluate whether glial and neuronal GlyT1 have distinct roles at inhibitory synapses, we inactivated the GlyT1 gene cell type-specifically using mice carrying floxed GlyT1 alleles GlyT1((+)/+)). GlyT1((+)/(+)) mice expressing Cre recombinase in glial cells developed severe neuromotor deficits during the first postnatal week, which mimicked the phenotype of conventional GlyT1 knock-out mice and are consistent with glycinergic over-inhibition. In contrast, Cre-mediated inactivation of the GlyT1 gene in neuronal cells did not result in detectable motor impairment. Notably, some animals deficient for glial GlyT1 survived the first postnatal week and did not develop neuromotor deficits throughout adulthood, although GlyT1 expression was efficiently reduced. Thus, glial GlyT1 is critical for the regulation of glycine levels at inhibitory synapses only during early postnatal life.
authors.affiliation: Department for Neurochemistry, Max-Planck Institute for Brain Research, Deutschordenstrasse 46, 60529 Frankfurt, Germany. Volker.Eulenburg@biochem.uni-erlangen.de
authors.forename: Volker
authors.initials: V
authors.lastname: Eulenburg
authors.forename: Marina
authors.initials: M
authors.lastname: Retiounskaia
authors.forename: Theofilos
authors.initials: T
authors.lastname: Papadopoulos
authors.forename: Jesús
authors.initials: J
authors.lastname: Gomeza
authors.forename: Heinrich
authors.initials: H
authors.lastname: Betz
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D001933:Brain Stem / Q000254:growth & development / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D020820:Dyskinesias / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D013116:Spinal Cord / Q000254:growth & development / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C493267:Slc6a9 protein, mouse