Abstract
A decrease in expression of the glutamate transporter GLT-1 is thought to be responsible for the increase in extracellular glutamate observed in patients with amyotrophic lateral sclerosis (ALS) and in a transgenic mouse model of ALS. We examined protein levels of the glutamate transporters GLT-1, GLAST and EAAC1 in the G93A (SOD1) transgenic mouse model of ALS. GLT-1 was detected in two bands (72 and 150 kD). Semi-quantitative analysis of Western blots showed that GLT-1 levels in sensorimotor cortex, brain stem, and cervical and lumbar spinal cord of G93A mice did not differ significantly from controls, either at end stage or at 60- or 90-days old. Nevertheless, other differences were found in GLT-1 at end stage. The percentage of total GLT-1 in the 150 kD band increased significantly (p<0.05) in the spinal cord and was elevated in the brain stem and cortex. Furthermore, brain stem and spinal cord GLT-1 from G93A mice showed retarded mobility on gels compared to controls (M(r) approximately equal to 77.3+/-2.3 and 164.3+/-3.1 vs. 72.2+/-2.4 and 153.6+/-4.7, respectively). GLAST and EAAC1 were unchanged in both amount and mobility. These results show that a loss of GLT-1 protein is not necessary for ALS-like neurodegeneration in G93A mice. However, the changes in GLT-1 mobility and distribution indicate that GLT-1 is altered in mice with the SOD1 mutation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / genetics
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Aging / metabolism
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Amino Acid Transport System X-AG / genetics
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Amino Acid Transport System X-AG / metabolism
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Amyotrophic Lateral Sclerosis / metabolism*
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Amyotrophic Lateral Sclerosis / pathology
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Amyotrophic Lateral Sclerosis / physiopathology
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Central Nervous System / metabolism*
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Central Nervous System / pathology
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Central Nervous System / physiopathology
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Dimerization
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Disease Models, Animal
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Electrophoresis, Polyacrylamide Gel / methods
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Excitatory Amino Acid Transporter 1
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Excitatory Amino Acid Transporter 2 / genetics*
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Excitatory Amino Acid Transporter 2 / metabolism*
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Excitatory Amino Acid Transporter 3
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Female
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Glutamate Plasma Membrane Transport Proteins
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Glutamic Acid / metabolism*
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Humans
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Immunohistochemistry
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Male
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Mice
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Mice, Transgenic
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Molecular Weight
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Motor Neurons / pathology
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Muscle Weakness / genetics
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Muscle Weakness / pathology
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Mutation / genetics*
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Phenotype
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Superoxide Dismutase / genetics*
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Superoxide Dismutase / metabolism
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Superoxide Dismutase-1
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Symporters*
Substances
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Amino Acid Transport System X-AG
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Carrier Proteins
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Excitatory Amino Acid Transporter 1
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Excitatory Amino Acid Transporter 2
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Excitatory Amino Acid Transporter 3
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Glutamate Plasma Membrane Transport Proteins
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SLC1A1 protein, human
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SLC1A3 protein, human
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SOD1 protein, human
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Slc1a1 protein, mouse
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Slc1a3 protein, mouse
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Symporters
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Glutamic Acid
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Sod1 protein, mouse
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Superoxide Dismutase
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Superoxide Dismutase-1