PMID- 16830212 OWN - NLM STAT- MEDLINE DCOM- 20061003 LR - 20181113 IS - 0364-3190 (Print) IS - 0364-3190 (Linking) VI - 31 IP - 7 DP - 2006 Jul TI - Reversed actrocytic GLT-1 during ischemia is crucial to excitotoxic death of neurons, but contributes to the survival of astrocytes themselves. PG - 933-43 AB - During ischemia, the operation of astrocytic/neuronal glutamate transporters is reversed and glutamate and Na(+) are co-transported to the extracellular space. This study aims to investigate whether this reversed operation of glutamate transporters has any functional meanings for astrocytes themselves. Oxygen/glucose deprivation (OGD) of neuron/astrocyte co-cultures resulted in the massive death of neurons, and the cell death was significantly reduced by treatment with either AP5 or DHK. In cultured astrocytes with little GLT-1 expression, OGD produced Na(+) overload, resulting in the reversal of astrocytic Na(+)/Ca(2+)-exchanger (NCX). The reversed NCX then caused Ca(2+) overload leading to the damage of astrocytes. In contrast, the OGD-induced Na(+) overload and astrocytic damage were significantly attenuated in PACAP-treated astrocytes with increased GLT-1 expression, and the attenuation was antagonized by treatment with DHK. These results suggested that the OGD-induced reversal of GLT-1 contributed to the survival of astrocytes themselves by releasing Na(+) with glutamate via reversed GLT-1. FAU - Kosugi, Tatsuro AU - Kosugi T AD - Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan. FAU - Kawahara, Koichi AU - Kawahara K LA - eng PT - Journal Article DEP - 20060708 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Excitatory Amino Acid Transporter 2) SB - IM MH - Animals MH - Astrocytes/*metabolism MH - Brain Ischemia/*metabolism MH - *Cell Survival MH - Coculture Techniques MH - Excitatory Amino Acid Transporter 2/*metabolism MH - Immunohistochemistry MH - Neurons/metabolism MH - Rats EDAT- 2006/07/11 09:00 MHDA- 2006/10/04 09:00 CRDT- 2006/07/11 09:00 PHST- 2006/06/05 00:00 [accepted] PHST- 2006/07/11 09:00 [pubmed] PHST- 2006/10/04 09:00 [medline] PHST- 2006/07/11 09:00 [entrez] AID - 10.1007/s11064-006-9099-6 [doi] PST - ppublish SO - Neurochem Res. 2006 Jul;31(7):933-43. doi: 10.1007/s11064-006-9099-6. Epub 2006 Jul 8.