Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, 44, Toreza prospekt, 194223 Saint Petersburg, Russia.
Int J Mol Sci. 2019 Nov 21;20(23):5852. doi: 10.3390/ijms20235852.
Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20-30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.
癫痫是一种常见的神经障碍。尽管有多种抗癫痫药物可供使用，但这些药物在 20-30%的患者中无法预防癫痫发作。因此，迫切需要新的药理学策略来控制癫痫发作。谷氨酸摄取的调节可能在治疗耐药性癫痫形式方面具有潜力。以前的研究表明，抗生素头孢曲松（CTX）增加了兴奋性氨基酸转运体 2（EAAT2）的表达和功能活性，并产生了相当大的抗惊厥作用。然而，其他研究并未证实 CTX 给药具有显著的抗惊厥作用。我们研究了 CTX 治疗对年轻雄性 Wistar 大鼠 EAAT 表达和谷氨酸能神经传递以及其抗惊厥作用的影响。如定量实时聚合酶链反应（qPCR）测定和 Western blot 分析所示，CTX 治疗后海马体中 EAAT2 的 mRNA 而非蛋白质水平增加。重复 CTX 给药仅对戊四氮（PTZ）诱导的惊厥在最大电休克阈值测试（MEST）中具有轻度的抗惊厥作用。CTX 处理不会影响谷氨酸能神经传递，包括突触效能、短期易化或海马体和颞叶皮质中兴奋性突触后电位（EPSP）的总和。然而，它降低了由强烈电刺激引起的场 EPSP（fEPSP）幅度。总之，在幼鼠中，CTX 处理不会诱导 EAAT2 的过表达，因此仅产生微弱的抗惊厥作用。我们的数据为调节 EAAT2 表达对大脑功能的影响提供了新的见解。
