TY - JOUR
T1 - Glial glutamate transporter GLT-1 down-regulation precedes delayed neuronal death in gerbil hippocampus following transient global cerebral ischemia
AU - Raghavendra Rao, Vemuganti L.
AU - Muralikrishna Rao, Adibhatla
AU - Dogan, Aclan
AU - Bowen, Kellie K.
AU - Hatcher, James
AU - Rothstein, Jeffrey D.
AU - Dempsey, Robert J.
N1 - Funding Information:
Funded by the American Heart Association Wisconsin Affiliate (9806376X), American Heart Association National (9950086N), University of Wisconsin-Madison Medical School Research Committee (161-9587) to VLRR and National Institute of Health (NS28000 and NS31220) to RJD.
PY - 2000/5
Y1 - 2000/5
N2 - Glial (GLT-1 and GLAST) and neuronal (EAAC1) high-affinity transporters mediate the sodium dependent glutamate reuptake in mammalian brain. Their dysfunction leads to neuronal damage by allowing glutamate to remain in the synaptic cleft for a longer duration. The purpose of the present study is to understand their contribution to the ischemic delayed neuronal death seen in gerbil hippocampus following transient global cerebral ischemia. The protein levels of these three transporters were studied by immunoblotting as a function of reperfusion time (6 h to 7 days) following a 10 min occlusion of bilateral common carotid arteries in gerbils. In the vulnerable hippocampus, there was a significant decrease in the protein levels of GLT-1 (by 36-46%, P<0.05; between 1 and 3 days of reperfusion) and EAAC1 (by 42-68%, P<0.05; between 1 and 7 days of reperfusion). Histopathological evaluation showed no neuronal loss up to 2 days of reperfusion but an extensive neuronal loss (by ~84%, P<0.01) at 7 days of reperfusion in the hippocampal CA1 region. The time frame of GLT-1 dysfunction (1-3 days of reperfusion) precedes the initiation of delayed neuronal death (2-3 days of reperfusion). This suggests GLT-1 dysfunction as a contributing factor for the hippocampal neuronal death following transient global cerebral ischemia. Furthermore, decreased EAAC1 levels may contribute to GABAergic dysfunction and excitatory/inhibitory imbalance following transient global ischemia. Copyright (C) 2000.
AB - Glial (GLT-1 and GLAST) and neuronal (EAAC1) high-affinity transporters mediate the sodium dependent glutamate reuptake in mammalian brain. Their dysfunction leads to neuronal damage by allowing glutamate to remain in the synaptic cleft for a longer duration. The purpose of the present study is to understand their contribution to the ischemic delayed neuronal death seen in gerbil hippocampus following transient global cerebral ischemia. The protein levels of these three transporters were studied by immunoblotting as a function of reperfusion time (6 h to 7 days) following a 10 min occlusion of bilateral common carotid arteries in gerbils. In the vulnerable hippocampus, there was a significant decrease in the protein levels of GLT-1 (by 36-46%, P<0.05; between 1 and 3 days of reperfusion) and EAAC1 (by 42-68%, P<0.05; between 1 and 7 days of reperfusion). Histopathological evaluation showed no neuronal loss up to 2 days of reperfusion but an extensive neuronal loss (by ~84%, P<0.01) at 7 days of reperfusion in the hippocampal CA1 region. The time frame of GLT-1 dysfunction (1-3 days of reperfusion) precedes the initiation of delayed neuronal death (2-3 days of reperfusion). This suggests GLT-1 dysfunction as a contributing factor for the hippocampal neuronal death following transient global cerebral ischemia. Furthermore, decreased EAAC1 levels may contribute to GABAergic dysfunction and excitatory/inhibitory imbalance following transient global ischemia. Copyright (C) 2000.
KW - Delayed neuronal death
KW - Gerbil
KW - Global cerebral Ischemia
KW - Glutamate transporters
KW - Hippocampus
KW - Immunoblotting
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U2 - 10.1016/S0197-0186(99)00153-9
DO - 10.1016/S0197-0186(99)00153-9
M3 - Article
C2 - 10762090
AN - SCOPUS:0033969456
SN - 0197-0186
VL - 36
SP - 531
EP - 537
JO - Neurochemistry International
JF - Neurochemistry International
IS - 6
ER -