The functional role of glutamate transporter associated protein (GTRAP3-18) in epileptogenesis

谷氨酸转运蛋白相关蛋白 (GTRAP3-18) 在癫痫发生中的功能作用

• 批准号: 17591223
• 负责人: DOI Taku
• 金额: $ 1.98万
• 依托单位: University of Miyazaki
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591223/
• 关键词: epilepsy; glutamate; GABA; transporter; GTRAP3-18; addicsin

EAAC-1 functions in the re-uptake of extracellular glutamate that leads to synthesis of GABA. Knockdown of EAAC-1 by anti-sense induces convulsive seizures in rats. Glutamate transporter associated protein 3-18 (GTRAP3-18) suppresses the binding affinity of glutamate with EAAC1 on the neuron. We undertook this study to evaluate the contribution of GTRAP3-18 in the PTZ kindling. Rats were injected with GTRAP3-18 anti-sense oligonucleotide into lateral ventricle, after that the animals were administered i.p. three times per week with PTZ (40 mg/kg) until they were fully kindled. Measurement of hippocampal glutamate and GABA transporters and glutamate receptors by western blot showed that GLT-1, GAT-3, GluR1, G1uR2, NMDAR1 were decreased significantly at 24 hours in fully kindled GTRAP3-18 knockdown compared to control (injected sense oligonucleotide and fully kindled). PTZ seizure duration was significantly prolonged, latency more brief and kindling onset earlier when compared to control animals. The microdialysis study show that hippocampal glutamate and GABA basal release in GTRAP3-18 knockdown group higher rather than those of senseinjected group. These observations suggest that GTRAP3-18 may affect development of epileptogenesis.

EAAC-1参与细胞外谷氨酸的重新摄取，从而导致GABA的合成。反义敲除EAAC-1诱导大鼠惊厥发作谷氨酸转运体相关蛋白3-18(GTRAP3-18)抑制谷氨酸与神经元上EAAC1的结合。我们开展了这项研究，以评估GTRAP3-18在PTZ点燃中的贡献。大鼠侧脑室注射GTRAP3-18反义寡核苷酸后，ip。每周三次注射PTZ(40 mg/kg)，直到完全点燃。免疫印迹法检测GTRAP3-18基因敲除大鼠海马谷氨酸转运体、谷氨酸转运体和谷氨酸受体的表达，结果显示，GTRAP3-18基因敲除后24小时，GLT-1、GAT-3、GluR1、G1uR2、NMDAR1的表达均显著低于对照组(注射正义寡核苷酸和完全点燃)。与对照组相比，PTZ惊厥持续时间显著延长，潜伏期更短，点燃开始时间更早。微透析研究表明，GTRAP3-18基因敲除组大鼠海马谷氨酸和GABA的基础释放量高于正义注射组。这些观察结果提示GTRAP3-18可能影响癫痫的发生发展。

项目成果

Functional role of GABA transporters for kindling development in GLAST KO mice.

GABA 转运蛋白对 GLAST KO 小鼠点燃发育的功能作用。

• 发表时间: 2007
• 期刊: Neurosci Res 57(2)
• 作者: Nagatomo;K.;Ueda;Y.;Doi;T.;Takaki;M.;Tsuru;N
• 通讯作者: N

扁桃核キンドリングにおける海馬レドックス均衡の脆弱性と評価方法

杏仁核点燃海马氧化还原平衡的脆弱性及评价方法

• 发表时间: 2005
• 期刊: てんかん研究 23
• 作者: 植田勇人;横山秀克;中島暉;土井拓;長友慶子
• 通讯作者: 長友慶子

Protective role of pentobarbital pretreatment for NMDA-R activated lipid peroxidation is derived from the synergistic effect on endogenous anti-oxidant in the hippocampus of rats.

戊巴比妥预处理对 NMDA-R 激活的脂质过氧化的保护作用源自对大鼠海马内源性抗氧化剂的协同作用。

• 发表时间: 2007
• 期刊: Neuroscience letter 417
• 作者: Y.Ueda;T.Doi;K.Nagatomo;A.Nakajima
• 通讯作者: A.Nakajima

In vivo evaluation of the effect of zonisamide on the hippocampal redox state during kainic acid-induced seizure status in rats.

体内评估唑尼沙胺对红藻氨酸诱导的大鼠癫痫发作状态期间海马氧化还原状态的影响。

• 发表时间: 2005
• 期刊: Neurochemical Research Vol. 30, No. 9
• 作者: Ueda;Y;Doi;T.;Tokumaru;J.;Yokoyama;H.;Nakajima;A.;Nagatomo;K.
• 通讯作者: K.

The functional role of glutamatetransporter associated protein (GTRAP3-18) in epileptogenesis induced by PTZ-kindling

谷氨酸转运蛋白相关蛋白（GTRAP3-18）在PTZ点燃诱发癫痫发生中的功能作用

• 发表时间: 2006
• 期刊: Epilepsia 47, S4
• 作者: Y.Ueda;T.Doi.;K.Nagatomo;M.Takaki;A.Nakajima;L.J.Willmore
• 通讯作者: L.J.Willmore