Transgenic SOD1 G93A mice develop reduced GLT-1 in spinal cord without alterations in cerebrospinal fluid glutamate levels

Caterina Bendotti, Massimo Tortarolo, Sachin K. Suchak, Novella Calvaresi, Lucia Carvelli, Antonio Bastone, Massimo Rizzi, Marcus Rattray, Tiziana Mennini

Research output: Contribution to journalArticle

Abstract

Glutamate-induced excitotoxicity is suggested to play a central role in the development of amyotrophic lateral sclerosis (ALS), although it is still unclear whether it represents a primary cause in the cascade leading to motor neurone death. We used western blotting, immunocytochemistry and in situ hybridization to examine the expression of GLT-1 in transgenic mice carrying a mutated (G93A) human copper-zinc superoxide dismutase (TgSOD1 G93A), which closely mimic the features of ALS. We observed a progressive decrease in the immunoreactivity of the glial glutamate transporter (GLT-1) in the ventral, but not in the dorsal, horn of lumbar spinal cord. This effect was specifically found in 14- and 18-week-old mice that had motor function impairment, motor neurone loss and reactive astrocytosis. No changes in GLT-1 were observed at 8 weeks of age, before the appearance of clinical symptoms. Decreases in GLT-1 were accompanied by increased glial fibrillary acidic protein (GFAP) levels and no change in the levels of GLAST, another glial glutamate transporter. The glutamate concentration in the cerebrospinal fluid (CSF) of TgSOD1 G93A mice was not modified at any of the time points examined, compared with age-matched controls. These findings indicate that the loss of GLT-1 protein in ALS mice selectively occurs in the areas affected by neurodegeneration and reactive astrocytosis and it is not associated with increases of glutamate levels in CSF. The lack of changes in GLT-1 at the presymptomatic stage suggests that glial glutamate transporter reduction is not a primary event leading to motor neurone loss.

Original languageEnglish
Pages (from-to)737-746
Number of pages10
JournalJournal of Neurochemistry
Volume79
Issue number4
DOIs
Publication statusPublished - 2001

Keywords

  • Excitotoxicity
  • Glial fibrillary acidic protein
  • Motor neurones
  • Superoxide dismutase-1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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