Mohammadi Moslem, Zare Zohreh, Allah-Moradi Esmaeil, Vaezi Narges, Valadan Reza, Tehrani Mohsen
Department of Physiology & Pharmacology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Anatomical Sciences, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Neurotoxicology. 2016 Dec;57:251-257. doi: 10.1016/j.neuro.2016.10.009. Epub 2016 Oct 18.
Organophosphates affect brain function through a variety of mechanisms beyond their shared role as cholinesterase inhibitors. The aim of the current study was to investigate the changes in the expression of glial (GLAST and GLT-1) and neuronal (EAAC1) glutamate transporters at mRNA and protein levels in paraoxon-treated rat hippocampus. Adult male Wistar rats were intraperitoneally treated with either vehicle (corn oil) or one of three dosages of paraoxon (0.3, 0.7 or 1mg/kg). After 4 or 18h, both hippocampi of each rat were collected to detect mRNA and protein expression of glutamate transporters using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. Animals treated with 0.3mg/kg paraoxon showed no difference in mRNA and protein levels of the glutamate transporters when compared with control group. At 4h after exposure with 0.7 and 1mg/kg paraoxon, the expression of GLAST and GLT-1 increased at mRNA and protein levels and remained elevated after 18h. No difference in the expression of EAAC1 at mRNA and protein levels was observed in any paraoxon-treated groups compared with the control group. This study showed an increased expression of glial (GLAST and GLT-1), but not neuronal (EAAC1) glutamate transporters, in adult rat hippocampus following administration of convulsive dosages of paraoxon. These suggest a protective and compensatory adaptation for effective uptake of glutamate in hippocampus induced by paraoxon and thus attenuating seizure activity.
有机磷酸酯通过多种机制影响脑功能，这些机制超出了它们作为胆碱酯酶抑制剂的共同作用。本研究的目的是调查对氧磷处理的大鼠海马体中胶质细胞（谷氨酸转运体GLAST和GLT-1）和神经元（EAAC1）谷氨酸转运体在mRNA和蛋白质水平上的表达变化。成年雄性Wistar大鼠腹腔注射赋形剂（玉米油）或三种剂量对氧磷（0.3、0.7或1mg/kg）之一。4小时或18小时后，分别收集每只大鼠的双侧海马体，使用定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹法检测谷氨酸转运体的mRNA和蛋白质表达。与对照组相比，用0.3mg/kg对氧磷处理的动物在谷氨酸转运体的mRNA和蛋白质水平上没有差异。在暴露于0.7和1mg/kg对氧磷4小时后，GLAST和GLT-1的表达在mRNA和蛋白质水平上增加，并在18小时后保持升高。与对照组相比，在任何对氧磷处理组中均未观察到EAAC1在mRNA和蛋白质水平上的表达差异。本研究表明，在给予惊厥剂量的对氧磷后，成年大鼠海马体中胶质细胞（GLAST和GLT-1）而非神经元（EAAC1）谷氨酸转运体的表达增加。这些结果表明对氧磷诱导的海马体中谷氨酸有效摄取存在保护性和代偿性适应，从而减轻癫痫活动。
