GLT-1 glutamate transporter levels are unchanged in mice expressing G93A human mutant SOD1

J Neurol Sci. 2002 Jan 15;193(2):117-26. doi: 10.1016/s0022-510x(01)00656-6.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Amino Acid Transport System X-AG / genetics
  • Amino Acid Transport System X-AG / metabolism
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology
  • Central Nervous System / physiopathology
  • Dimerization
  • Disease Models, Animal
  • Electrophoresis, Polyacrylamide Gel / methods
  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2 / genetics*
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Excitatory Amino Acid Transporter 3
  • Female
  • Glutamate Plasma Membrane Transport Proteins
  • Glutamic Acid / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Weight
  • Motor Neurons / pathology
  • Muscle Weakness / genetics
  • Muscle Weakness / pathology
  • Mutation / genetics*
  • Phenotype
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Symporters*

Substances

  • Amino Acid Transport System X-AG
  • Carrier Proteins
  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2
  • Excitatory Amino Acid Transporter 3
  • Glutamate Plasma Membrane Transport Proteins
  • SLC1A1 protein, human
  • SLC1A3 protein, human
  • SOD1 protein, human
  • Slc1a1 protein, mouse
  • Slc1a3 protein, mouse
  • Symporters
  • Glutamic Acid
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1