title: Reversed actrocytic GLT-1 during ischemia is crucial to excitotoxic death of neurons, but contributes to the survival of astrocytes themselves.
abstract: 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.
authors.affiliation: Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kosugi
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawahara
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002470:Cell Survival; D018920:Coculture Techniques; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism; D051381:Rats
chemical_list: D027342:Excitatory Amino Acid Transporter 2