Hirao T, Morimoto K, Yamamoto Y, Watanabe T, Sato H, Sato K, Sato S, Yamada N, Tanaka K, Suwaki H
Department of Neuropsychiatry, Faculty of Medicine, Kagawa Medical University, Japan.
Brain Res Mol Brain Res. 1998 Feb;54(1):49-55. doi: 10.1016/s0169-328x(97)00323-9.
To investigate the role played by GABA transporters in epileptic seizures, we examined time-dependent and regional changes in expression of GAT-1 and GAT-3 GABA transporter mRNA in amygdala-kindled rat brain using an in situ hybridization method. GAT-1 mRNA was significantly increased bilaterally in the hippocampal dentate gyrus (111-116%) at 1 h after kindled generalized seizures. GAT-1 mRNA was also significantly increased bilaterally in the hippocampal subfields (CA1-4 and dentate gyrus [110-117%]) at 4 h after kindled seizures. There were no significant changes in GAT-1 mRNA level in the amygdalar nuclei, pyriform cortex or cerebral cortex either ipsilaterally or contralaterally at any time after kindled seizures. In contrast, GAT-3 mRNA was significantly increased bilaterally in the amygdalar nuclei and in the contralateral pyriform cortex and cerebral cortex 1 h after seizures. Since all these changes returned to control levels by 8 or 24 h after kindled seizures, the increases in GABA transporter mRNA appeared to be transient responses to seizure activity. These findings indicate that GAT-1 subtype transporter is specifically involved in seizure activity in the hippocampus, while GAT-3 subtype transporter is mainly involved in seizure activity in the amygdalar nuclei and pyriform cortex following amygdala-kindled generalized seizures.
为研究γ-氨基丁酸(GABA)转运体在癫痫发作中所起的作用,我们采用原位杂交法检测了杏仁核点燃大鼠脑中GAT-1和GAT-3 GABA转运体mRNA表达的时间依赖性和区域变化。在点燃全身性癫痫发作后1小时,海马齿状回双侧的GAT-1 mRNA显著增加(111 - 116%)。在点燃癫痫发作后4小时,海马各亚区(CA1 - 4和齿状回[110 - 117%])双侧的GAT-1 mRNA也显著增加。在点燃癫痫发作后的任何时间,杏仁核、梨状皮质或大脑皮质同侧或对侧的GAT-1 mRNA水平均无显著变化。相比之下,癫痫发作后1小时,杏仁核双侧以及对侧梨状皮质和大脑皮质的GAT-3 mRNA显著增加。由于在点燃癫痫发作后8或24小时所有这些变化均恢复到对照水平, GABA转运体mRNA的增加似乎是对癫痫活动的短暂反应。这些发现表明,GAT-1亚型转运体特别参与海马中的癫痫活动,而GAT-3亚型转运体在杏仁核点燃全身性癫痫发作后主要参与杏仁核和梨状皮质中的癫痫活动。