Corticosterone exacerbates cyanide-induced cell death in hippocampal cultures: role of astrocytes.
Previous study demonstrated that, in hippocampal neuron/glia mixed cultures, glucocorticoids (GCs) enhanced extracellular overflow of [3H]D-aspartate [3H]D-Asp) by decreasing its uptake, thereby aggravating cell death during cyanide-induced ischemia. Since neuronal and glial cells respond to ischemic insult and GC differently, this study further evaluated the relative significance of these cells in GC endangering ischemic cell death. Using D-[2,3-3H]aspartic acid ([3H]D-Asp) as a tracer, it was found that corticosterone (CORT, the physiological GC in rat) enhanced the overflow of extracellular [3H]D-Asp in astrocyte cultures and, to a lesser extent, in neuron-enriched cultures during cyanide-induced ischemia. Analysis of [3H]D-Asp uptake kinetics indicates that CORT reduced the maximum uptake rate in cultured astrocyte, but not in neurons, after cyanide exposure. It is concluded that, during cyanide-induced ischemia, CORT might mainly the ability of astrocytes to clear excitatory amino acids from the synapse, thus exacerbating the damaging cascade of these amino acids.
Chou
Y C
YC
Institute of Physiology, National Yang-Ming University, Taipei, Taiwan, Republic of China. YCJCHOU@YM.EDU.TW
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D003486:Cyanides / Q000633:toxicity*; D004357:Drug Synergism; D005333:Fetus; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D003486:Cyanides; D014316:Tritium; D001224:Aspartic Acid; D003345:Corticosterone