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Tardive decrease of astrocytic glutamate transporter protein in transgenic mice with ALS-linked mutant SOD1.

H Warita1, Y Manabe, T Murakami

  • 1Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, Japan.

Neurological Research
|September 20, 2002
PubMed
Summary
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Glutamate transporter EAAT2 levels remain stable during early paralysis in SOD1 mice, suggesting it is not a primary factor in motor neuron death. EAAT2 and GFAP show distinct expression patterns in the spinal cord.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss.
  • Mutations in superoxide dismutase 1 (SOD1) are a known cause of familial ALS.
  • Glutamate excitotoxicity, mediated by impaired glutamate transport, is implicated in ALS pathogenesis.

Purpose of the Study:

  • To investigate the expression patterns of glutamate transporter proteins EAAT2 and EAAT3 in the spinal cord of a mouse model of ALS.
  • To examine the relationship between EAAT2 and GFAP expression in the ventral horn during disease progression.
  • To determine the role of EAAT2 in motoneuron degeneration in the G93A SOD1 mouse model.

Main Methods:

  • Immunocytochemistry was used to examine the expression of glutamate transporter proteins (EAAT2, EAAT3) and glial fibrillary acidic protein (GFAP) in the spinal cord of G93A SOD1 transgenic mice.

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  • Expression levels were analyzed at different stages of the disease, including pre-symptomatic, paralytic, and terminal stages.
  • Main Results:

    • Astroglial EAAT2 protein levels were maintained in the ventral horn until the terminal stage of the disease, despite the onset of paralysis.
    • Neuronal EAAT3 protein levels decreased concurrently with EAAT2 at the terminal stage.
    • Glial fibrillary acidic protein (GFAP) immunoreactivity showed a progressive increase from 25 weeks of age, indicating reactive astrogliosis.
    • Dissociative expression patterns between EAAT2 and GFAP were observed in the ventral horn.

    Conclusions:

    • The findings suggest that EAAT2 is not an early or primary contributor to motoneuron death in the G93A SOD1 mouse model.
    • The observed dissociation between EAAT2 and GFAP expression highlights complex glial responses in ALS.
    • Further research is needed to elucidate the precise mechanisms of motoneuron degeneration in this ALS model.