Diespirov Georgy P, Postnikova Tatyana Y, Griflyuk Alexandra V, Kovalenko Anna A, Zaitsev Aleksey V
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, St. Petersburg, 194223, Russia.
Biochemistry (Mosc). 2023 Mar;88(3):353-363. doi: 10.1134/S0006297923030057.
Status epilepticus (SE) triggers many not yet fully understood pathological changes in the nervous system that can lead to the development of epilepsy. In this work, we studied the effects of SE on the properties of excitatory glutamatergic transmission in the hippocampus in the lithium-pilocarpine model of temporal lobe epilepsy in rats. The studies were performed 1 day (acute phase), 3 and 7 days (latent phase), and 30 to 80 days (chronic phase) after SE. According to RT-qPCR data, expression of the genes coding for the AMPA receptor subunits GluA1 and GluA2 was downregulated in the latent phase, which may lead to the increased proportion of calcium-permeable AMPA receptors that play an essential role in the pathogenesis of many CNS diseases. The efficiency of excitatory synaptic neurotransmission in acute brain slices was decreased in all phases of the model, as determined by recording field responses in the CA1 region of the hippocampus in response to the stimulation of Schaffer collaterals by electric current of different strengths. However, the frequency of spontaneous excitatory postsynaptic potentials increased in the chronic phase, indicating an increased background activity of the glutamatergic system in epilepsy. This was also evidenced by a decrease in the threshold current causing hindlimb extension in the maximal electroshock seizure threshold test in rats with temporal lobe epilepsy compared to the control animals. The results suggest a series of functional changes in the properties of glutamatergic system associated with the epilepsy development and can be used to develop the antiepileptogenic therapy.
癫痫持续状态（SE）会引发许多尚未完全了解的神经系统病理变化，这些变化可能导致癫痫的发展。在这项研究中，我们在大鼠颞叶癫痫的锂-匹罗卡品模型中，研究了SE对海马体中兴奋性谷氨酸能传递特性的影响。研究在SE后的1天（急性期）、3天和7天（潜伏期）以及30至80天（慢性期）进行。根据RT-qPCR数据，编码AMPA受体亚基GluA1和GluA2的基因表达在潜伏期下调，这可能导致钙通透性AMPA受体比例增加，而钙通透性AMPA受体在许多中枢神经系统疾病的发病机制中起着重要作用。通过记录海马体CA1区对不同强度电流刺激Schaffer侧支的场反应来确定，在模型的所有阶段，急性脑片中兴奋性突触神经传递的效率均降低。然而，在慢性期，自发性兴奋性突触后电位的频率增加，这表明癫痫中谷氨酸能系统的背景活动增强。在颞叶癫痫大鼠中，与对照动物相比，最大电休克惊厥阈值试验中引起后肢伸展的阈值电流降低，这也证明了这一点。结果表明，谷氨酸能系统特性存在一系列与癫痫发展相关的功能变化，并可用于开发抗癫痫发生疗法。
