2024-03-28T14:13:39Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/146102022-11-17T02:08:08Zhdl_2115_20053hdl_2115_145Reversed actrocytic GLT-1 during ischemia is crucial to excitotoxic death of neurons, but contributes to the survival of astrocytes themselves.Kosugi, TatsuroKawahara, KoichiIschemiaReversed GLT-1Astrocyte damageNa+/Ca2+ exchangerExcitotoxic neuronal death491.3During 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.Springer NetherlandsJournal Articleapplication/pdfhttp://hdl.handle.net/2115/14610https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/14610/1/NR2006-31-7.pdf0364-31901573-6903Neurochemical Research3179339432006-07enginfo:pmid/16830212info:doi/10.1007/s11064-006-9099-6The original publication is available at www.springerlink.comauthor