Increase in glutamate-induced neurotoxicity by activated astrocytes involves stimulation of protein kinase C

• Verfasst von: Ahlemeyer, Barbara [VerfasserIn]
• Verfasst von: Kölker, Stefan [VerfasserIn]
• Verfasst von: Zhu, Yuan [VerfasserIn]
• Verfasst von: Hoffmann, Georg F. [VerfasserIn]
• Verfasst von: Krieglstein, Josef [VerfasserIn]
• Titel: Increase in glutamate-induced neurotoxicity by activated astrocytes involves stimulation of protein kinase C
• Verf.angabe: Barbara Ahlemeyer, Stefan Kölker, Yuan Zhu, Georg F. Hoffmann, Josef Krieglstein
• E-Jahr: 2002
• Jahr: 24 July 2002
• Umfang: 12 S.
• Fussnoten: Gesehen am 28.12.2020
• Titel Quelle: Enthalten in: Journal of neurochemistry
• Ort Quelle: Oxford : Wiley-Blackwell, 1956
• Jahr Quelle: 2002
• Band/Heft Quelle: 82(2002), 3, Seite 504-515
• ISSN Quelle: 1471-4159
• DOI: doi:10.1046/j.1471-4159.2002.00994.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: glutamate transporter
• Sach-SW: hippocampal neurones
• Sach-SW: NMDA
• Sach-SW: NR1-NR2A subtype
• Sach-SW: NR1-NR2B subtype
• Sach-SW: phorbol esters
• K10plus-PPN: 1743564406

Abstract

Activation of astrocytes is a common feature of neurological disorders, but the importance of this phenomenon for neuronal outcome is not fully understood. Treatment of mixed hippocampal cultures of neurones and astrocytes from day 2-4 in vitro (DIV 2-4) with 1 µm cytosine arabinofuranoside (AraC) caused an activation of astrocytes as detected by a stellate morphology and a 10-fold increase in glial fibrillary acidic protein (GFAP) level compared with vehicle-treated cultures. After DIV 12, we determined 43% and 97% damaged neurones 18 h after the exposure to glutamate (1 mm, 1 h) in cultures treated with vehicle and AraC, respectively. Dose-response curves were different with a higher sensitivity to glutamate in cultures treated with AraC (EC50 = 0.01 mm) than with vehicle (EC50 = 0.12 mm). The susceptibility of neurones to 1 mm glutamate did not correlate with the percentage of astrocytes and was insensitive to an inhibition of glutamate uptake. In cultures treated with vehicle and AraC, glutamate-induced neurotoxicity was mediated through stimulation of the NR1-NR2B subtype of NMDA receptors, because it was blocked by the NMDA receptor antagonist MK-801 and the NR1-NR2B selective receptor antagonist ifenprodil. Protein levels of the NR2A and NR2B subunits of NMDA receptor were similar in cultures treated with vehicle or AraC. AraC-induced changes in glutamate-induced neurotoxicity were mimicked by activation of protein kinase C (PKC), whereas neuronal susceptibility to glutamate was reduced in cultures depleted of PKC and treated with AraC suggesting that the increase in glutamate toxicity by activated astrocytes involves activation of PKC.