Functional significance of the preconditioning-induced down-regulation of glutamate transporter GLT-1 in neuron/astrocyte co-cultures.
In the brain, prior sublethal ischemia (preconditioning, PC) is known to produce tolerance of neurons to subsequent lethal ischemia. This study aims at elucidating what alterations were induced in neurons and/or astrocytes by PC treatment. The rise in the extracellular concentration of glutamate during ischemia was markedly suppressed by the prior PC treatment. Immunocytochemical and Western blot analyses demonstrated that the expression of the astrocytic glutamate transporter GLT-1 was transiently down-regulated after the PC insult. The PC insult possibly suppressed the neuron-derived factors up-regulating GLT-1. Here we show that PC-induced down-regulation of GLT-1 is crucial for the increased neuronal resistance to subsequent severe ischemic insult.
Kosugi
Tatsuro
T
Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, 060-0814, Sapporo, Japan.
Kawahara
Koichi
K
Yamada
Takeshi
T
Nakajima
Takayuki
T
Tanaka
Motoki
M
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D019194:Ischemic Preconditioning; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats
D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid