title: Decreased expression of Ras-GRF1 in the brain tissue of the intractable epilepsy patients and experimental rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhu
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Peng
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000502:physiology; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism*; D014015:Tissue Banks; D055815:Young Adult; D020666:ras-GRF1 / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; C513039:RASGRF1 protein, human; C525926:Rasgrf1 protein, rat; D020666:ras-GRF1