Glutamate release induced by activation of glycine and GABA transporters in spinal cord is enhanced in a mouse model of amyotrophic lateral sclerosis

Autor: Maurizio Raiteri, Luca Raiteri, Simona Zappettini, Giambattista Bonanno, Silvio Paluzzi, Sara Stigliani
Rok vydání: 2005
Předmět:
medicine.medical_specialty
GABA Plasma Membrane Transport Proteins
animal structures
DNA
Complementary
animal diseases
SOD1
Excitotoxicity
Glutamic Acid
Mice
Transgenic
Toxicology
medicine.disease_cause
chemistry.chemical_compound
Mice
Superoxide Dismutase-1
Glycine Plasma Membrane Transport Proteins
Internal medicine
medicine
GABA transporter
Animals
Humans
biology
Amyotrophic lateral sclerosisSOD1-G93A(+) miceGlutamate releaseGlycine heterotransportersGABA heterotransportersRelease mechanisms
Superoxide Dismutase
General Neuroscience
Amyotrophic Lateral Sclerosis
Glutamate receptor
nutritional and metabolic diseases
Long-term potentiation
Strychnine
GABA receptor antagonist
nervous system diseases
Endocrinology
nervous system
Biochemistry
chemistry
Spinal Cord
Glycine
biology.protein
Algorithms
Synaptosomes
Zdroj: Neurotoxicology. 26(5)
ISSN: 0161-813X
Popis: Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease, involving both upper and lower motor neurons, the cause of which is obscure, although glutamate (GLU)-induced excitotoxicity has been suggested to play a major role. We studied the release of [3H]d-aspartate ([3H]d-ASP) and endogenous glutamate evoked by glycine (GLY) or GABA from spinal cord synaptosomes in mice expressing a mutant form of human SOD1 with a Gly93Ala substitution ([SOD1-G93A(+)]), a transgenic model of amyotrophic lateral sclerosis, in mice expressing the non-mutated form of human SOD1 [SOD1+], and in non-transgenic littermates [SOD1(-)/G93A(-)]. In parallel experiments, we also studied the release of [3H]GABA evoked by GLY and that of [3H]GLY evoked by GABA. Mutant mice were killed at advanced phase of pathology or during the pre-symptomatic period. In SOD1(-)/G93A(-) or SOD1(+) mice GLY evoked [3H]d-ASP and [3H]GABA release, while GABA caused [3H]d-ASP, but not [3H]GLY, release. The GLY-evoked release of [3H]d-ASP, but not that of [3H]GABA, and the GABA-evoked [3H]d-ASP release, but not that of [3H]GLY, were more pronounced in SOD1-G93A(+) than in SOD1(+) or SOD1(-)/G93A(-) mice. Furthermore, the excessive potentiation of [3H]d-ASP by GLY or GABA was already present in asymptomatic 30-40 day-old SOD1-G93A(+) mice. The releases of endogenous glutamate and GABA also were enhanced by GLY and the GLY-evoked release of endogenous glutamate, but not of endogenous GABA, was higher in SOD1-G93A(+) than in control animals. Potentiation of the spontaneous amino acid release is likely to be mediated by activation of a GLY or a GABA transporter, since the effect of GLY was counteracted by the GLY transporter blocker glycyldodecylamide but not by the GLY receptor antagonists strychnine and 5,7-dichlorokynurenate while the effect of GABA was diminished by the GABA transporter blocker SKF89976-A but not by the GABA receptor antagonists SR9531 and CGP52432. It is concluded that the glutamate release machinery seems excessively functional in SOD1-G93A(+) animals.
Databáze: OpenAIRE
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