Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain.
Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain.
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DOI：
10.1046/j.1460-9568.2001.01367.x
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
V. Rao;A. Dogan;K. Bowen;K. Todd;R. Dempsey;R. Dempsey
中科院分区：
文献类型：
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作者：
V. Rao;A. Dogan;K. Bowen;K. Todd;R. Dempsey;R. Dempsey
可控性皮质撞击(CCI)致大鼠脑创伤可导致海马区慢性神经元死亡。在正常大脑中，谷氨酸转运体主动清除突触释放的谷氨酸，以防止受体过度激活和兴奋性毒性。谷氨酸转运体1(GLT-1)是谷氨酸转运体中含量最丰富、活性最高的转运体，参与谷氨酸的大量摄取。与对侧或假手术对照组相比，CCI损伤后24~72h，同侧海马区GLT-1mRNA和蛋白水平显著降低(分别下降49~66%，P<；0.05)和29~44%(P<；0.05)。与GLT-1正义/随机ODN组相比，GLT-1反义寡核苷酸(ODN)组大鼠CCI损伤加重了海马神经元的死亡和死亡率。损伤后7d，GLT-1反义ODN组大鼠海马神经元数量在CA1区(减少32%，P<0.05)、CA2区(减少45%，P<0.01)、CA3区(减少68%，P<0.01)和齿状回区(减少31%，P<0.05)明显低于GLT-1正义/随机ODN组。本研究提示GLT-1功能障碍在创伤性脑损伤后海马神经元死亡中起促进作用。
Traumatic injury to rat brain induced by controlled cortical impact (CCI) 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. CCI 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. CCI 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.