Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1G93A mice

Andrea C. Pardo, Victor Wong, Leah M. Benson, Margaret Dykes, Kohichi Tanaka, Jeffrey D. Rothstein, Nicholas J. Maragakis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


Recent studies have highlighted the role of astrocytes in the development of motor neuron disease in animal models. The astrocyte glutamate transporter GLT1 is responsible for a significant portion of glutamate transport from the synaptic cleft; regulating synaptic transmission and preventing glutamate excitotoxicity. While previous studies have demonstrated reductions in GLT1 with SOD1-mediated disease progression, it is not well established whether a reduction in this astrocyte-specific transporter alters the pathobiology of motor neuron degeneration in the SOD1G93A mouse. In order to address this possible astrocyte-specific influence, we crossed the SOD1G93A mouse line with a mouse heterozygous for GLT1 (GLT1±) exhibiting a significant reduction in transporter protein. Mice that carried both the SOD1 mutation and a reduced amount of GLT1 (SOD1G93A/GLT1±) exhibited an increase in the rate of motor decline accompanied by earlier motor neuron loss when compared with SOD1G93A mice. A modest reduction in survival was also noted in these mice. Dramatic losses of the GLT1 protein and reduced glutamate transport in the lumbar spinal cords of the SOD1G93A/GLT1± animals were also observed. GLT1 was not significantly changed in cortices from these animals suggesting that the effect of mutant SOD1 on GLT1 production/function was largely targeted to spinal cord rather than cortical astrocytes. This study suggests that astrocytes, and the astrocyte glutamate transporter GLT1, play a role in modifying disease progression and motor neuron loss in this model.

Original languageEnglish (US)
Pages (from-to)120-130
Number of pages11
JournalExperimental Neurology
Issue number1
StatePublished - Sep 2006

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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