title: GLT-1 glutamate transporter levels are unchanged in mice expressing G93A human mutant SOD1.
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.
authors.affiliation: Department of Neurology, MCP Hahnemann University, MS 423, 245 North 15th Street, Philadelphia, PA 19102-1192, USA. deitch@drexel.edu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Deitch
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Alexander
authors.forename: Luis
authors.initials: L
authors.lastname: Del Valle
authors.forename: Terry D
authors.initials: TD
authors.lastname: Heiman-Patterson
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019281:Dimerization; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics* / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3; D005260:Female; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008970:Molecular Weight; D009046:Motor Neurons / Q000473:pathology; D018908:Muscle Weakness / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D027981:Symporters
chemical_list: D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; C493400:SLC1A1 protein, human; C493394:SLC1A3 protein, human; C000606290:SOD1 protein, human; C493399:Slc1a1 protein, mouse; C493393:Slc1a3 protein, mouse; D027981:Symporters; D018698:Glutamic Acid; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1