Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia

Tu Hsueh Yeh, Hwa Min Hwang, Jin Jung Chen, Tony Wu, Allen Hon Lun Li, Hung Li Wang

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Astroglial glutamate transporters, GLT-1 and GLAST, play an essential role in removing released glutamate from the extracellular space and are essential for maintaining a low concentration of extracellular glutamate in the brain. It was hypothesized that impaired function of glial glutamate transporters induced by transient global ischemia may lead to an elevated level of extracellular glutamate and subsequent excitotoxic neuronal death. To test this hypothesis, in the present study, we performed whole-cell patch-clamp recording of hippocampal CA1 astrocytes in control or postischemic slices, and measured glutamate transporter activity by recording glutamate-evoked transporter currents. Six to 24 h after global ischemia, maximal amplitude of glutamate transporter currents recorded from postischemic CA1 astrocytes was significantly reduced. Western blotting analysis indicated that transient global ischemia decreased the protein level of GLT-1 in the hippocampal CA1 area without affecting GLAST protein level. Further real-time quantitative RT-PCR assays showed that global ischemia resulted in a decrease in GLT-1 mRNA level of hippocampal CA1 region. Global ischemia-induced reduction in GLT-1 expression and glutamate transporter function of CA1 astrocytes precedes the initiation of delayed neuronal death in CA1 pyramidal layer. The present study provides the evidence that transient global ischemia downregulates glutamate transporter function of hippocampal CA1 astrocytes by decreasing mRNA and protein levels of GLT-1.

Original languageEnglish
Pages (from-to)476-483
Number of pages8
JournalNeurobiology of Disease
Volume18
Issue number3
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Astrocytes
Ischemia
Glutamic Acid
Hippocampal CA1 Region
Messenger RNA
Proteins
Extracellular Space
Neuroglia
Real-Time Polymerase Chain Reaction
Down-Regulation
Western Blotting
Brain

Keywords

  • CA1 astrocyte
  • GLAST transporter
  • GLT1 transporter
  • Glutamate transporter
  • Ischemia
  • Transporter current

ASJC Scopus subject areas

  • Neurology

Cite this

Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia. / Yeh, Tu Hsueh; Hwang, Hwa Min; Chen, Jin Jung; Wu, Tony; Li, Allen Hon Lun; Wang, Hung Li.

In: Neurobiology of Disease, Vol. 18, No. 3, 04.2005, p. 476-483.

Research output: Contribution to journalArticle

Yeh, Tu Hsueh ; Hwang, Hwa Min ; Chen, Jin Jung ; Wu, Tony ; Li, Allen Hon Lun ; Wang, Hung Li. / Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia. In: Neurobiology of Disease. 2005 ; Vol. 18, No. 3. pp. 476-483.
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