Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
Int J Dev Neurosci. 2023 Dec;83(8):703-714. doi: 10.1002/jdn.10298. Epub 2023 Sep 1.
Epileptogenesis can be associated with altered genetic control of the GABAergic system. Here we analyzed Krushinsky-Molodkina (KM) rats genetically prone to audiogenic epilepsy. KM rats express fully formed audiogenic seizures (AGSs) not early, then they reach 3 months. At the age of 1-2 months, KM rats either do not express AGS or demonstrate an incomplete pattern of seizure. Such long-term development of AGS susceptibility makes KM rats an especially convenient model to investigate the mechanisms and dynamics of the development of inherited epilepsy. The analysis of the GABAergic system of the hippocampus of KM rats was done during postnatal development at the 15th, 60th, and 120th postnatal days. Wistar rats of corresponding ages were used as a control. In the hippocampus of KM pups, we observed a decrease in the expression of glutamic acid decarboxylase 67 (GAD67) and parvalbumin (PV), which points to a decrease in the activity of GABAergic neurons. Analysis of the 2-month-old KM rats showed an increase in GAD67 and PV expression while synapsin I and vesicular GABA transporter (VGAT) were decreased. In adult KM rats, the expression of GAD67, PV, and synapsin I was upregulated. Altogether, the obtained data indicate significant alterations in GABAergic transmission in the hippocampus of audiogenic KM rats during the first postnatal months.
癫痫发生可能与 GABA 能系统的遗传控制改变有关。在这里,我们分析了遗传性听觉癫痫易感性的 Krushinsky-Molodkina (KM) 大鼠。KM 大鼠表现出完全形成的听觉性癫痫发作 (AGS) 不是早期,而是在 3 个月时达到。在 1-2 个月大时,KM 大鼠要么不表现出 AGS,要么表现出不完全的发作模式。这种长期的 AGS 易感性发展使 KM 大鼠成为研究遗传性癫痫发展机制和动力学的特别方便的模型。在生后发育的第 15、60 和 120 天,对 KM 大鼠海马体的 GABA 能系统进行了分析。相应年龄的 Wistar 大鼠作为对照。在 KM 幼鼠的海马体中,我们观察到谷氨酸脱羧酶 67 (GAD67) 和钙结合蛋白 parvalbumin (PV) 的表达减少,这表明 GABA 能神经元的活性降低。对 2 月龄 KM 大鼠的分析表明,GAD67 和 PV 的表达增加,而突触素 I 和囊泡 GABA 转运体 (VGAT) 减少。在成年 KM 大鼠中,GAD67、PV 和突触素 I 的表达上调。总之,这些数据表明,在听觉性 KM 大鼠的海马体中,GABA 能传递在生后第一个月发生了显著改变。