Downregulation of glutamate transporters is associated with elevation in extracellular glutamate concentration following rat microsphere embolism

Feng Han, Norifumi Shioda, Shigeki Moriguchi, Zheng Hong Qin, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Sodium-dependent glutamate transporters expressed in astroglial cells and neurons are essential for clearance of extracellular glutamate. In the present study, we found elevation of extracellular glutamate concentration associated with concomitant downregulation of glutamate transporters following rat microsphere embolism (ME). A marked increase in extracellular glutamate in the rat striatum was observed by microdialysis immediately after ME induction, and glutamate remained elevated at least 12 h after ischemia. Concomitantly, impairment of high KCl (146 mM)-induced glutamate release was observed in the striatum 12 h after ME. Consistent with the persistent increase in extracellular glutamate, expression of the glutamate transporters EAAC1 and GLT-1 significantly decreased 6 h after insult without a change in GLAST levels. GLT-1 expression was restored to basal levels within 48 h, whereas EAAC1 expression remained decreased up to at least 72 h after ME. Restoration of GLT-1 was associated with increased expression of the astroglial marker GFAP, whereas markedly reduced EACC1 levels were correlated with reduced levels of the neuronal marker MAP2, likely due to loss of vulnerable neurons. Taken together, downregulation of glutamate transporters after ME is associated with dysregulation of basal glutamate concentrations and KCl-induced glutamate release in the brain.

Original languageEnglish
Pages (from-to)275-280
Number of pages6
JournalNeuroscience Letters
Volume430
Issue number3
DOIs
Publication statusPublished - 2008 Jan 17

Keywords

  • Glutamate
  • Glutamate transporter
  • Microdialysis
  • Microsphere embolism
  • Microtubule-associated protein 2

ASJC Scopus subject areas

  • Neuroscience(all)

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