HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Information Science and Technology / Faculty of Information Science and Technology >
Peer-reviewed Journal Articles, etc >

Selective blockade of astrocytic glutamate transporter GLT-1 with dihydrokainate prevents neuronal death during ouabain treatment of astrocyte/neuron cocultures

Files in This Item:
GLIA40-3.pdf2.11 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/5937

Title: Selective blockade of astrocytic glutamate transporter GLT-1 with dihydrokainate prevents neuronal death during ouabain treatment of astrocyte/neuron cocultures
Authors: Kawahara, Koichi1 Browse this author →KAKEN DB
Hosoya, Rui Browse this author
Sato, Hideomi Browse this author
Tanaka, Motoki Browse this author
Nakajima, Takayuki Browse this author
Iwabuchi, Sadahiro Browse this author
Authors(alt): 河原, 剛一1
Keywords: glutamate neurotoxicity
dihydrokainate
Na+/K+-ATPase
Issue Date: Dec-2002
Publisher: Wiley-Liss, Inc.
Journal Title: Glia
Volume: 40
Issue: 3
Start Page: 337
End Page: 349
Publisher DOI: 10.1002/glia.10133
PMID: 12420313
Abstract: Glutamate (Glu) is a major excitatory neurotransmitter of the mammalian central nervous system and under normal conditions plays an important role in information processing in the brain. Therefore, extracellular Glu is subject to strong homeostasis. Astrocytes in the brain have been considered to be mainly responsible for the clearance of extracellular Glu. In this study, using mixed neuron/astrocyte cultures, we investigated whether astrocytic Glu transporter GLT-1 is crucial to the survival of neurons under various conditions. Treatment of the mixed cultures with a low concentration of Glu did not produce significant death of neurons. However, cotreatment with dihydrokainate (DHK), a specific blocker of GLT-1, resulted in significant neuronal death that was suppressed by an antagonist of N-methyl-D-aspartate (NMDA) receptors. These results suggested that astrocytic GLT-1 participated in the clearance of extracellular Glu and protected neurons from NMDA receptor-mediated toxicity. When the cultures were treated with ouabain, an inhibitor of Na+/K+-ATPase, a low concentration of Glu resulted in massive neuronal death that was also suppressed by cotreatment with an antagonist of NMDA receptors. In this case, however, cotreatment with DHK significantly protected neurons from death, suggesting that GLT-1 was responsible for the death of neurons. The present study provides evidence suggesting that astrocytes use their Glu transporter GLT-1 to protect neurons from Glu toxicity, but, ironically, also use GLT-1 to kill neurons through Glu toxicity depending on their status.
Rights: Copyright © 2003 John Wiley & Sons, Inc., Glia, vol.40-3, p. 337-349
Relation: http://www.interscience.wiley.com/
Type: article (author version)
URI: http://hdl.handle.net/2115/5937
Appears in Collections:情報科学院・情報科学研究院 (Graduate School of Information Science and Technology / Faculty of Information Science and Technology) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 河原 剛一

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

Feedback - Hokkaido University