Department of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, No. 32, Western Section 2nd Part of 1st Ring Road, Chengdu Sichuan 610072, China.
Brain Res. 2013 Feb 1;1493:99-109. doi: 10.1016/j.brainres.2012.11.033. Epub 2012 Nov 27.
Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) is present mainly at synaptosome and its expression after birth increases in parallel with the development of neuronal circuitry. Evidences suggested that Ras-GRF1 could mediate forms of synaptic plasticity and might participate in the regulation of neuronal excitability and neurite outgrowth though various signal transduction pathway. The aim of this study was to measure Ras-GRF1 expression in brain tissue of patients with drug-refractory temporal lobe epilepsy (TLE) and lithium chloride-pilocarprine kindled rats using double-label immunofluorescence, immunohistochemistry and Western blotting and to discuss the possible role of Ras-GRF1 in TLE. We randomly selected 30 temporal neocortices tissues from patients with TLE and 9 histologically normal temporal neocortices samples from controls. Meanwhile, we investigated the distribution and level of Ras-GRF1 protein expression during the different phases (the acute period, the latent period and the chronic phase) in the epileptic and control rats. Ras-GRF1 was mainly expressed in the plasma membrane and dendrite of neurons, but it was not co-expressed with GFAP-positive astrocytes in the brain tissue of patients and epileptic rats. Compared with controls, Ras-GRF1 expression was significantly decreased in TLE patients. Ras-GRF1 expression in epileptic rats was already reduced at 1 day post-seizures, then gradually decreased during the latent period and reached a minimum level during the chronic phase. These results demonstrated that the decreased expression of Ras-GRF1 could be involved in the pathogenesis of human TLE.
Ras 鸟嘌呤核苷酸释放因子 1（Ras-GRF1）主要存在于突触体中，其表达在出生后与神经元回路的发育平行增加。有证据表明，Ras-GRF1 可以通过各种信号转导途径介导突触可塑性的形式，并可能参与神经元兴奋性和神经突生长的调节。本研究旨在通过双标免疫荧光、免疫组织化学和 Western blot 检测难治性颞叶癫痫（TLE）患者和氯化锂-毛果芸香碱点燃大鼠脑组织中 Ras-GRF1 的表达，并探讨 Ras-GRF1 在 TLE 中的可能作用。我们随机选择了 30 例 TLE 患者的颞叶新皮质组织和 9 例对照组织的正常颞叶新皮质组织。同时，我们研究了 Ras-GRF1 蛋白在癫痫大鼠不同阶段（急性期、潜伏期和慢性期）的分布和表达水平。Ras-GRF1 主要表达于神经元的质膜和树突中，但在癫痫患者和大鼠的脑组织中并不与 GFAP 阳性星形胶质细胞共表达。与对照组相比，TLE 患者 Ras-GRF1 的表达显著降低。癫痫大鼠的 Ras-GRF1 表达在发作后 1 天即已降低，随后在潜伏期逐渐降低，并在慢性期达到最低水平。这些结果表明，Ras-GRF1 表达的减少可能参与了人类 TLE 的发病机制。
