open access

https://hdl.handle.net/2115/14610

Reversed actrocytic GLT-1 during ischemia is crucial to excitotoxic death of neurons, but contributes to the survival of astrocytes themselves.

英語

Excitotoxic neuronal death

2006-07

Springer Netherlands

Neurochemical Research

31(7)

933-943

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+/Ca2+-exchanger (NCX). The reversed NCX then caused Ca2+ 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.

学術雑誌論文

Accepted Manuscript

The original publication is available at www.springerlink.com

0364-3190

1573-6903