Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury.
Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury.
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DOI：
10.1002/glia.21241
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发表时间：
2011-12
期刊：
影响因子：
6.2
通讯作者：
Maragakis, Nicholas J.
中科院分区：
文献类型：
--
作者：
Lepore, Angelo C.;O'Donnell, John;Kim, Andrew S.;Yang, Eun Ju;Tuteja, Alisha;Haidet-Phillips, Amanda;O'Banion, Colin P.;Maragakis, Nicholas J.
星形胶质细胞谷氨酸转运蛋白GLT 1负责成人中枢神经系统（CNS）中绝大多数谷氨酸摄取，从而调节细胞外谷氨酸稳态并防止兴奋性毒性。谷氨酸失调在创伤性脊髓损伤（SCI）的预后中起着重要作用。为了确定GLT 1在SCI后继发性细胞丢失中的作用，GLT 1星形胶质细胞谷氨酸转运蛋白（GLT 1 +/−）杂合子小鼠和野生型小鼠接受胸部挤压SCI。与野生型对照组相比，GLT 1 +/−小鼠的后肢运动功能恢复减弱，病变大小增加，组织保留减少。与野生型小鼠相比，GLT 1 +/−小鼠的椎管内GLT 1蛋白和功能性谷氨酸摄取减少，并伴有挤压损伤后细胞凋亡和神经元丢失增加。这些结果表明，星形胶质细胞GLT 1在限制SCI后的二次细胞死亡中发挥作用，并且还表明关键星形胶质细胞功能的损害对创伤性中枢神经系统损伤后的结果具有显着影响。这些发现还表明，增加椎管内GLT 1表达可能代表SCI治疗的治疗相关靶点。
The astrocyte glutamate transporter, GLT1, is responsible for the vast majority of glutamate uptake in the adult central nervous system (CNS), thereby regulating extracellular glutamate homeostasis and preventing excitotoxicity. Glutamate dysregulation plays a central role in outcome following traumatic spinal cord injury (SCI). To determine the role of GLT1 in secondary cell loss following SCI, mice heterozygous for the GLT1 astrocyte glutamate transporter (GLT1+/−) and wild-type mice received thoracic crush SCI. Compared to wild-type controls, GLT1+/− mice had an attenuated recovery in hindlimb motor function, increased lesion size, and decreased tissue sparing. GLT1+/− mice showed a decrease in intraspinal GLT1 protein and functional glutamate uptake compared to wild-type mice, accompanied by increased apoptosis and neuronal loss following crush injury. These results suggest that astrocyte GLT1 plays a role in limiting secondary cell death following SCI, and also show that compromise of key astrocyte functions has significant effects on outcome following traumatic CNS injury. These findings also suggest that increasing intraspinal GLT1 expression may represent a therapeutically relevant target for SCI treatment.
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通讯作者：
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