Fattorini Giorgia, Melone Marcello, Bragina Luca, Candiracci Chiara, Cozzi Andrea, Pellegrini Giampietro Domenico E, Torres-Ramos Monica, Pérez-Samartín Alberto, Matute Carlos, Conti Fiorenzo
Dipartimento di Neuroscienze, Università Politecnica delle Marche, Ancona, Italy.
Glia. 2008 Sep;56(12):1320-7. doi: 10.1002/glia.20700.
Using western blottings, microdialysis, and functional assays we tested the hypothesis that phencyclidine (PCP) modifies the expression and function of glutamate (Glu) transporters in the rat frontal cortex. Western blotting studies revealed that administration of PCP (10 mg/kg/day; 7 days) increased significantly the expression of the astrocytic Glu transporter GLT-1/EAAT2. Functional studies showed that PCP increased significantly Na+-dependent Glu uptake in slices and in neuron/astrocyte co-cultures, and microdialysis studies evidenced that PCP treatment reduced basal Glu output. In our experimental conditions, PCP did not induce toxicity. These studies show that PCP increases the expression of GLT-1 in the cerebral cortex, thereby increasing Glu uptake and reducing extracellular [Glu].
我们使用蛋白质免疫印迹法、微透析法和功能测定法,检验了苯环己哌啶(PCP)改变大鼠额叶皮质中谷氨酸(Glu)转运体表达和功能这一假说。蛋白质免疫印迹研究表明,给予PCP(10毫克/千克/天;7天)可显著增加星形胶质细胞Glu转运体GLT-1/EAAT2的表达。功能研究显示,PCP可显著增加切片及神经元/星形胶质细胞共培养物中Na+依赖的Glu摄取,微透析研究证明PCP处理可降低基础Glu输出。在我们的实验条件下,PCP未诱导毒性。这些研究表明,PCP可增加大脑皮质中GLT-1的表达,从而增加Glu摄取并降低细胞外[Glu]。