Activation of a glycine transporter on spinal cord neurons causes enhanced glutamate release in a mouse model of amyotrophic lateral sclerosis.
The release of [(3)H]D-aspartate ([(3)H]D-ASP) or [(3)H]GABA evoked by glycine from spinal cord synaptosomes was compared in mice expressing mutant human SOD1 with a Gly(93) Ala substitution ([SOD1-G93A(+)]), a transgenic model of amyotrophic lateral sclerosis, and in control mice. Mice expressing mutated SOD1 were killed at the advanced phase of the pathology, when they showed signs of ingestion disability, because of paralysis of the posterior limbs. In control mice glycine concentration-dependently evoked [(3)H]D-ASP and [(3)H]GABA release. Potentiation of the spontaneous release of both amino acids is likely to be mediated by activation of a glycine transporter, since the effects of glycine were counteracted by the glycine transporter blocker glycyldodecylamide but not by the glycine receptor antagonists strychnine and 5,7-dichlorokynurenate. The glycine-evoked release of [(3)H]D-ASP, but not that of [(3)H]GABA, was significantly more pronounced in SOD1-G93A(+) than in control animals.
Raiteri
Luca
L
Department of Experimental Medicine, Pharmacology and Toxicology Section, University of Genoa, Viale Cembrano 4, 16148 Genova, Italy.
Paolucci
Egle
E
Prisco
Simona
S
Raiteri
Maurizio
M
Bonanno
Giambattista
G
D000367:Age Factors; D026921:Amino Acid Transport Systems, Neutral / Q000502:physiology*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D026603:D-Aspartic Acid / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000494:pharmacology; D050487:Glycine Plasma Membrane Transport Proteins; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D026921:Amino Acid Transport Systems, Neutral; D050487:Glycine Plasma Membrane Transport Proteins; C000606290:SOD1 protein, human; D014316:Tritium; D018698:Glutamic Acid; D026603:D-Aspartic Acid; D005680:gamma-Aminobutyric Acid; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005998:Glycine