Nematipour Sara, Vahidinia Zeinab, Nejati Majid, Naderian Homayon, Beyer Cordian, Azami Tameh Abolfazl
Anatomical Sciences Research Center, Institute for Basic Sciences,Kashan University of Medical Sciences, Kashan, Iran.
Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2020 Oct;23(10):1346-1352. doi: 10.22038/ijbms.2020.48090.11039.
Glutamate is the most widespread neurotransmitter in the central nervous system and has several functions as a neuromodulator in the brain although in pathological conditions like ischemia it is excessively released causing cell death. Under physiological conditions, glutamate is rapidly scavenged from the synaptic cleft by excitatory amino-acid transporters (EAATs). An imbalance in glutamatergic neurotransmission could influence the expression of glutamate transporters and is a pathological feature in several neurological disorders. It has been shown that estrogen and progesterone act as neuroprotective agents after brain injury. This study aims to investigate the role of hormone therapy after middle cerebral artery occlusion (tMCAO) in the expression of GLT-1 and EAAT3 as glutamate transporters.
Middle cerebral artery occlusion technique was performed in Wistar rats in order to induce focal cerebral ischemia. Estrogen, progesterone, and a combination of both hormones were injected subcutaneously in the early minutes of reperfusion. Sensorimotor functional tests were performed and infarct volume was calculated by TTC staining of brain section. Gene and protein expression of EAAT3 and GLT-1 were evaluated by RT-PCR, immunoblotting, and immunohistochemistry.
Behavioral scores were increased and infarct volume was reduced by hormone therapy. RT-PCR, immunoblotting, and immunohistochemistry data showed that the expression of GLT-1 and EAAT3 increased after ischemia. Also, estrogen and progesterone treatment enhanced mRNA and protein expression levels of GLT-1 and EAAT3 compared with ischemia.
Steroids may protect brain tissue against ischemia-induced tissue degeneration by decreasing extracellular glutamate levels through the induction of glutamate transporters.
谷氨酸是中枢神经系统中分布最广泛的神经递质，在大脑中作为神经调节剂具有多种功能，尽管在缺血等病理状态下它会过度释放导致细胞死亡。在生理条件下，谷氨酸通过兴奋性氨基酸转运体（EAATs）从突触间隙迅速清除。谷氨酸能神经传递的失衡可能影响谷氨酸转运体的表达，并且是几种神经系统疾病的病理特征。研究表明，雌激素和孕酮在脑损伤后可作为神经保护剂。本研究旨在探讨大脑中动脉闭塞（tMCAO）后激素治疗对谷氨酸转运体GLT-1和EAAT3表达的作用。
在Wistar大鼠中进行大脑中动脉闭塞技术以诱导局灶性脑缺血。在再灌注的早期几分钟皮下注射雌激素、孕酮以及两种激素的组合。进行感觉运动功能测试，并通过脑切片的TTC染色计算梗死体积。通过RT-PCR、免疫印迹和免疫组织化学评估EAAT3和GLT-1的基因和蛋白表达。
激素治疗使行为评分增加，梗死体积减小。RT-PCR、免疫印迹和免疫组织化学数据显示，缺血后GLT-1和EAAT3的表达增加。此外，与缺血组相比，雌激素和孕酮治疗增强了GLT-1和EAAT3的mRNA和蛋白表达水平。
类固醇可能通过诱导谷氨酸转运体降低细胞外谷氨酸水平，从而保护脑组织免受缺血诱导的组织变性。
