Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain

Vemuganti L.Raghavendra Rao, Aclan Dogan, Kellie K. Bowen, Kathryn G. Todd, Robert J. Dempsey

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Traumatic injury to rat brain induced by controlled cortical impact (CCl) results in chronic neuronal death in the hippocampus. In the normal brain, glutamate transporters actively clear the glutamate released synaptically to prevent receptor overactivation and excitotoxicity. Glutamate transporter 1 (GLT-1) is the most abundant and active glutamate transporter, which mediates the bulk of glutamate uptake. CCl injury significantly decreased GLT-1 mRNA (by 49-66%, P< 0.05) and protein (by 29-44%, P< 0.05) levels in the ipsilateral hippocampus, compared with either the respective contralateral hippocampus or the sham-operated control, 24-72 h after the injury. CCl injury in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) exacerbated the hippocampal neuronal death and mortality, compared with the GLT-1 sense/random ODN-infused controls. At 7 days after the injury, hippocampal neuronal numbers were significantly lower in the CA1 (reduced by 32%, P< 0.05), CA2 (by 45%, P< 0.01), CA3 (by 68%, P < 0.01) and dentate gyrus (by 31%, P< 0.05) in GLT-1 antisense ODN-infused rats, compared with the GLT-1 sense/random ODN-infused controls. This study suggested a role for GLT-1 dysfunction in promoting the hippocampal neuronal death after traumatic brain injury.

Original languageEnglish (US)
Pages (from-to)119-128
Number of pages10
JournalEuropean Journal of Neuroscience
Volume13
Issue number1
DOIs
StatePublished - Jan 30 2001
Externally publishedYes

Keywords

  • Antisense ODN
  • Controlled cortical impact injury
  • Glutamate uptake
  • Hippocampus
  • Knockdown
  • Neuronal death

ASJC Scopus subject areas

  • Neuroscience(all)

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