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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Effect of topiramate and dBcAMP on expression of the glutamate transporters GLAST and GLT-1 in astrocytes cultured separately, or together with neurons.
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Effect of topiramate and dBcAMP on expression of the glutamate transporters GLAST and GLT-1 in astrocytes cultured separately, or together with neurons.

机译：托吡酯和dBcAMP对单独培养或与神经元一起培养的星形胶质细胞中谷氨酸转运蛋白GLAST和GLT-1表达的影响。

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摘要

The mechanism of the antiepileptic drug topiramate is not fully understood, but interaction with the excitatory neurotransmission, e.g. glutamate receptors, is believed to be part of its anticonvulsant effect. The glutamate transporters GLAST and GLT-1 are responsible for the inactivation of glutamate as a neurotransmitter and it was therefore investigated if topiramate might affect the expression of GLAST and GLT-1 in astrocytes cultured separately or together with neurons. Since expression and membrane trafficking of glutamate transporters are affected by the protein kinase C system as well as by dBcAMP it was also investigated if these signalling pathways might play a role. In astrocyte cultures expressing mainly GLAST treatment with dBcAMP (0.25 mM) led to an increased expression of the total amount of GLAST as well as of its membrane association. The enhanced expression in the membrane was particularly pronounced for the oligomeric form of GLAST. No detectable effect on the expression of GLAST in astrocytes treated with topiramate in the presence and absence of protein kinase C activators or inhibitors was observed. Astrocytes co-cultured with neurons expressed both GLAST and GLT-1. In these cultures prolonged exposure to 30 muM topiramate (10 days) led to a statistically significant increase (P<0.025) in the membrane expression of GLAST. In case of GLT-1, culture in the presence of 30 microM topiramate for 1 and 10 days led to alterations in the total, cytoplamic and membrane expression of the oligomeric form of the transporter.
机译：抗癫痫药托吡酯的作用机理尚不完全清楚，但与兴奋性神经传递，例如神经兴奋性相互作用有关。谷氨酸受体被认为是其抗惊厥作用的一部分。谷氨酸转运蛋白GLAST和GLT-1负责使谷氨酸作为神经递质失活，因此研究了托吡酯是否会影响单独培养或与神经元一起培养的星形胶质细胞中GLAST和GLT-1的表达。由于谷氨酸转运蛋白的表达和膜运输受蛋白质激酶C系统以及dBcAMP的影响，因此还研究了这些信号通路是否可能起作用。在主要表达用dBcAMP（0.25 mM）进行GLAST处理的星形胶质细胞培养物中，GLAST总量及其膜结合的表达增加。对于GLAST的寡聚形式，膜中表达的增强特别明显。在存在和不存在蛋白激酶C激活剂或抑制剂的情况下，未观察到对用托吡酯处理的星形胶质细胞中GLAST表达的可检测影响。与神经元共培养的星形胶质细胞表达了GLAST和GLT-1。在这些培养物中，长时间暴露于30μM托吡酯（10天）导致GLAST膜表达在统计学上显着增加（P <0.025）。对于GLT-1，在30 microM托吡酯存在下培养1天和10天会导致转运蛋白的寡聚形式的总表达，细胞质表达和膜表达发生变化。

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