AMYGDALOID KINDLING IN GLUTAMATE TRANSPORTER (GLAST < GLT-1) KNOCKOUT MICE

谷氨酸转运蛋白 (GLAST < GLT-1) 敲除小鼠中的杏仁酸点燃

• 批准号: 12670946
• 负责人: TSURU Noriko
• 金额: $ 2.11万
• 依托单位: MIYAZAKI MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670946/
• 关键词: KINDLING; GLUTAMATE; TRANSPORTER; GLAST; TRANSGENIC; MOUSE; EPILEPTOGENESIS; EEG; kindling; transporter; transqeuic; amygdala; beta

Glutamate is a predominant excitatory neurotransmitter in the mammalian central nervous system. We previously reported the abnormal glutamate release during seizures following kindling. GLAST and GLT-1 are astrocytic glutamate transporters, highly concentrated in the cerebellum and the telencephalon, respectively. We have investigated whether stages of amygdala kindling in knockout (KO) mice deficient GLAST are the same as those of wild mice and whether there is secondary epileptogenesis. Method : Electrodes were implanted into the basolateral amygdala (B2.0, L3.0, H-4.5) in C57BL/6J mice and GLAST KO mice under the anesthesia. Once-daily stimulation of biphasic square pulse was applied through the stimulation electrodes. Results : The behavioral changes of the kindling in mice were : 1) arrest of behavior, 2) head nodding, 3) forelimb clonus, 4) dual forelimb clonus with rearing, 5) tonic generalized convulsion with elevation of tail, falling with GTC. There was a significant difference in the development of kindling. More stimulation was required for the kindling in GLAST deficient mice. There was no difference in the duration of AD between control and GLAST KO mice until the 16^<th> stimulations. However, the afterdischarges became slightly longer following overkindling in the control mice. The numbers of spikes at the stimulation point and secondary site in the GLAST KO mice were greater than those of control mice. These results suggest to us the GLAST (cerebellar glutamate transporter) may have a role in secondary epileptogenesis.

谷氨酸是哺乳动物中枢神经系统中一种主要的兴奋性神经递质。我们之前报道了点燃后癫痫发作期间谷氨酸的异常释放。GLAST和GLT-1是星形细胞谷氨酸转运体，分别在小脑和端脑中高度集中。我们研究了GLAST缺陷基因敲除(KO)小鼠杏仁核点燃的阶段是否与野生小鼠相同，以及是否存在继发性癫痫发生。方法：麻醉下将电极植入C57BL/6J小鼠和GLAST KO小鼠杏仁基底外侧核(B2.0、L3.0、H-4.5)。刺激电极采用双相方波脉冲刺激，每日1次。结果：点燃后小鼠的行为学改变为：1)行为停止，2)点头，3)前肢阵挛，4)双前肢阵挛，5)强直性全身性惊厥，尾部抬高，GTC倒下。在点燃的发展上有显著的差异。GLAST缺陷小鼠的点燃需要更多的刺激。在第16次刺激前，对照组和GLAST KO小鼠的AD持续时间无明显差异。然而，对照组小鼠在过度点燃后，后放电略有延长。GLAST KO组小鼠刺激点和次级部位的棘波数目明显多于对照组。这些结果提示GLAST(小脑谷氨酸转运体)可能在继发性癫痫发生中起作用。

项目成果

Tsuru N, Ueda Y, Doi T: "Amygdaloid kindling in mice and in Glutamate Transporter (GLAST) Knockout Mice -Discrepancy between the development, afterdischarge and epileptogenesis-"Epilepsia. (accepted). (2002)

Tsuru N、Ueda Y、Doi T：“小鼠和谷氨酸转运蛋白 (GLAST) 敲除小鼠中的杏仁核点燃 - 发育、放电后和癫痫发生之间的差异 -”癫痫。

Doi T, Ueda Y, Tsuru N, Tanaka K, Tokumaru J, Mitsuyama Y, Wilimore LJ:: "Ionotropic Glutamate receptor expression in GLAST knockout mice"Epilepsia. 41 Suppl.7. 27 (2000)

Doi T、Ueda Y、Tsuru N、Tanaka K、Tokumaru J、Mitsuyama Y、Wilimore LJ：：“GLAST 敲除小鼠中的离子型谷氨酸受体表达”癫痫。

Tsuru N.: "Secondary epileptogenesis in amygdaloid kindling in mice"Epilepsia. 41 Suppl. 7. 41-42 (2000)

Tsuru N.：“小鼠杏仁核点燃的继发性癫痫发生”癫痫。

Doi T, Ueda Y, Tsuru N, Tanaka K, Tokumaru J, Mitsuyama Y, Willmore LJ.: "Ionotropic Glutamate receptor expression in GLAST knockout mice"Epilepsia. 41 Suppl. 7. 27 (2000)

Doi T、Ueda Y、Tsuru N、Tanaka K、Tokumaru J、Mitsuyama Y、Willmore LJ.：“GLAST 敲除小鼠中的离子型谷氨酸受体表达”癫痫。

Tsuru N, Ueda Y.: "Early secondary epileptogenesis in the astroglial glutamate transporter (GLT- l) mouse"Epilepsia. 42 Suppl. 7. 228 (2001)

Tsuru N，Ueda Y.：“星形胶质细胞谷氨酸转运蛋白（GLT-1）小鼠的早期继发性癫痫发生”癫痫。