title: Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia.
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.
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Kwei-San, Tao-Yuan, Taiwan, ROC.
authors.forename: Tu-Hsueh
authors.initials: TH
authors.lastname: Yeh
authors.forename: Hwa-Min
authors.initials: HM
authors.lastname: Hwang
authors.forename: Jin-Jung
authors.initials: JJ
authors.lastname: Chen
authors.forename: Tony
authors.initials: T
authors.lastname: Wu
authors.forename: Allen H
authors.initials: AH
authors.lastname: Li
authors.forename: Hung-Li
authors.initials: HL
authors.lastname: Wang
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2