Neuron is the primary target of Ca2+ paradox-type insult-induced cell injury in neuron/astrocyte co-cultures.
"Ca(2+) paradox" is the phenomenon whereby the intracellular concentration of Ca(2+) paradoxically increases during reperfusion with normal Ca(2+)-containing media after brief exposure to a Ca(2+)-free solution. The present study aims to characterize the Ca(2+) paradox induced cell injury in neuron/astrocyte co-cultures. Prior exposure of the co-cultures to a low Ca(2+) solution for 60 min significantly injured only neurons after reperfusion with a normal Ca(2+) medium for 24h, but astrocytes remained intact. An analysis of the Ca(2+) paradox-induced changes in the intracellular concentration of Na(+) revealed that the concentration in astrocytes increased significantly during the reperfusion episode, resulting in a reversal of the operation of the astrocytic Na(+)-dependent glutamate transporter GLT-1. These results suggested that Ca(2+) paradox-induced accumulation of Na(+) in astrocytes was crucially involved in the excitotoxic neuronal injury resulting from the reversed astrocytic GLT-1 during the reperfusion episode. Previous studies have suggested that Ca(2+) paradox-induced injury in the brain occurs first in astroglial cells and only later in neurons resulting from the prior damage of astrocytes. Here we show that if "Ca(2+) paradox" occurs in the brain, neurons would be the primary target of Ca(2+) paradox-induced cell injury in the central nervous system.
Kosugi
Tatsuro
T
Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo 060-0814, Japan.
Kawahara
Koichi
K
Tanaka
Motoki
M
Watanabe
Yasuko
Y
Inanami
Osamu
O
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis / Q000235:genetics; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D012964:Sodium / Q000378:metabolism
D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D012964:Sodium; D019950:Mitogen-Activated Protein Kinase 1; D002118:Calcium