海人酸致大鼠海马结构GABA_B受体亚单位表达的研究  

Study on Expression of GABA_B Receptor Subunit in Hippocampus of KA-induced Epileptic Rats

作　　者：汤继宏[1] 包仕尧[2] 胡斯明[1] 

机构地区：[1]苏州大学附属儿童医院神经内科,215003 [2]苏州大学附属第二医院神经内科,215004

出　　处：《中国临床神经科学》2007年第4期364-369,共6页Chinese Journal of Clinical Neurosciences

摘　　要：目的:探讨海人酸诱导大鼠颞叶癫(EP)发作后2种γ-氨基丁酸(GABA)受体亚单位GABABR亚单位1a(GBR1a)和GABABR亚单位2(GBR2)在EP发生、发展中的作用。方法:运用原位杂交及免疫组化法,检测EP发作后GABABR亚单位mRNA及蛋白在海马的表达。结果:致早期CA1和CA3区2种亚单位mRNA表达持续低下后逐渐增加,DG区则暂时性下降后很快回升;而免疫反应早期却未见明显改变,随后CA1和CA3区表达处于低水平,DG区和颞叶皮质表达下降后很快恢复。结论:致后2种GABAB受体亚单位基因和蛋白表达上调为颞叶EP的内源性自我保护机制。Aim： To observe the dynamic changes in the expression of GABAB recepter （GABABR） subunits（GBRla and GBR2） in hippocampus following kainic acid induced （KA-induced） seizures, and to explore the possible molecular mechanisms of receptor subunit in temporal lobe epilepsy. Methods： In the basis of KA-induced temporal epileptic model, we determined GBRla and GBR2 mRNAs expression in hippocampus by the method of in situ hybridization and protein expression in hippocampus and temporal cortex（TC） by immunohistochemistry at control group and KA-induced seizure group at various time intervals. Results： In KA-induced epileptic rats, we found a early（6-12 h）widespread downregulation of both receptor subunits in hippocampal formation on the mRNA levels, then the decreases persisted in sectors CA1 and CA3, whereas mRNA levels in the granule cell layer increased rapidly and returned to control levels,and mRNA levels in sector CA3 partially recovered to control levels at late time points（30 d）. In epileptic rats, no prominent changes in GABABR irnmunoreactivities（GABABR-IR）at early time points after KA treatment were seen, unlike the decreases observed with GABABR mRNA. Soon afterwards,the reduction of GABABR-IR cells persisted in sectors CA1 and CA3. Whereas, after transient decrease, both subunit protein expression levels in DG and TC increased rapidly and significantly higher than that of control group at 1 day. However, the changes of both protein expression were not paralleled by the changes of both mRNA expression in hippocampus. Conclusion： The early decreases in GABABR mRNAs may be associated with epileptic susceptibility and maintenance of EP status.The subsequent decline in GABABR mRNA levels, however,is likely caused by neuronal losses in the hippocampus,but both subunit mRNA levels are partially recovered to control levels. This provides strong evidence for upregulation of GBRla and GBR2 surviving neurons in order to compensate for a loss in GABABR- mediated functions,and suggests

关 键 词：颞叶癫痫 GABAB受体 海马 海人酸 

分 类 号：R742.1[医药卫生—神经病学与精神病学]