TY - JOUR
T1 - Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain
AU - Rao, Vemuganti L.Raghavendra
AU - Dogan, Aclan
AU - Bowen, Kellie K.
AU - Todd, Kathryn G.
AU - Dempsey, Robert J.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Traumatic injury to rat brain induced by controlled cortical impact (CCl) results in chronic neuronal death in the hippocampus. In the normal brain, glutamate transporters actively clear the glutamate released synaptically to prevent receptor overactivation and excitotoxicity. Glutamate transporter 1 (GLT-1) is the most abundant and active glutamate transporter, which mediates the bulk of glutamate uptake. CCl injury significantly decreased GLT-1 mRNA (by 49-66%, P< 0.05) and protein (by 29-44%, P< 0.05) levels in the ipsilateral hippocampus, compared with either the respective contralateral hippocampus or the sham-operated control, 24-72 h after the injury. CCl injury in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) exacerbated the hippocampal neuronal death and mortality, compared with the GLT-1 sense/random ODN-infused controls. At 7 days after the injury, hippocampal neuronal numbers were significantly lower in the CA1 (reduced by 32%, P< 0.05), CA2 (by 45%, P< 0.01), CA3 (by 68%, P < 0.01) and dentate gyrus (by 31%, P< 0.05) in GLT-1 antisense ODN-infused rats, compared with the GLT-1 sense/random ODN-infused controls. This study suggested a role for GLT-1 dysfunction in promoting the hippocampal neuronal death after traumatic brain injury.
AB - Traumatic injury to rat brain induced by controlled cortical impact (CCl) results in chronic neuronal death in the hippocampus. In the normal brain, glutamate transporters actively clear the glutamate released synaptically to prevent receptor overactivation and excitotoxicity. Glutamate transporter 1 (GLT-1) is the most abundant and active glutamate transporter, which mediates the bulk of glutamate uptake. CCl injury significantly decreased GLT-1 mRNA (by 49-66%, P< 0.05) and protein (by 29-44%, P< 0.05) levels in the ipsilateral hippocampus, compared with either the respective contralateral hippocampus or the sham-operated control, 24-72 h after the injury. CCl injury in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) exacerbated the hippocampal neuronal death and mortality, compared with the GLT-1 sense/random ODN-infused controls. At 7 days after the injury, hippocampal neuronal numbers were significantly lower in the CA1 (reduced by 32%, P< 0.05), CA2 (by 45%, P< 0.01), CA3 (by 68%, P < 0.01) and dentate gyrus (by 31%, P< 0.05) in GLT-1 antisense ODN-infused rats, compared with the GLT-1 sense/random ODN-infused controls. This study suggested a role for GLT-1 dysfunction in promoting the hippocampal neuronal death after traumatic brain injury.
KW - Antisense ODN
KW - Controlled cortical impact injury
KW - Glutamate uptake
KW - Hippocampus
KW - Knockdown
KW - Neuronal death
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U2 - 10.1046/j.1460-9568.2001.01367.x
DO - 10.1046/j.1460-9568.2001.01367.x
M3 - Article
C2 - 11135010
AN - SCOPUS:0035176824
SN - 0953-816X
VL - 13
SP - 119
EP - 128
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 1
ER -