Successive alterations of hippocampal gamma-aminobutyric acid B receptor subunits in a rat model of febrile seizure
Successive alterations of hippocampal gamma-aminobutyric acid B receptor subunits in a rat model of febrile seizure
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DOI：
10.1016/j.lfs.2005.11.023
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发表时间：
2006-05-15
期刊：
影响因子：
6.1
通讯作者：
Yang, Zhi-Xian
中科院分区：
文献类型：
--
作者：
Han, Ying;Qin, Jiong;Yang, Zhi-Xian
热性惊厥是儿童期常见的惊厥类型。FS后脑功能的改变具有重要的临床意义。最近发现的γ-氨基丁酸B受体（GABA（B）R）是GABA的代谢型受体。本研究采用大鼠复发性FS模型，采用Western印迹、定量RT-PCR、双重免疫荧光、原位杂交和免疫沉淀/Western印迹等方法，研究复发性FS后海马GABA（B）R1 a和GABA（B）R2亚基的变化。在高温和诱导癫痫发作的情况下，每2 d 1次，共10次，最后一次治疗24 h后，海马GABA（B）R1 a和GABA（B）R2亚基含量降低。GABA（B）R2的下降持续30天以上。海马GABA（B）R1 a与GABA（B）R2的结合也在末次处理后24 h显著降低，并持续30 d以上。原位杂交显示，GABA（B）R1 a mRNA在齿状回明显减少，GABA（B）R2 mRNA在CA（3）区明显减少。在H-10和FS 1组中，热处理相同，但未诱导（H-10组）或仅诱导一次癫痫发作（FS 1组），也检测到GABA（B）R1 a和GABA（B）R2亚基的减少以及GABA（B）R1 a和GABA（B）R2亚基之间的结合能力降低，但严重程度较轻，从这些异常中恢复的时间较短。我们的结论是，GABA（B）R1 a和GABA（B）R2亚基和2个亚基的结合在未成年大鼠反复FS后的一个相对较长的时间内减少。这些变化可能导致海马兴奋/抑制功能的长期失衡，并源于反复热性惊厥的后果。(c)2005年爱思唯尔公司All rights reserved.
Febrile seizure (FS) is a frequently encountered seizure type in childhood. Changes of brain function following FS have clinical importance. The recently identified gamma-aminobutyric acid B receptor (GABA(B)R) is a metabotropic receptor of GABA. In this study, we used a rat model of recurrent FS to investigate the changes of GABA(B)R1a and GABA(B)R2 subunits in hippocampus after recurrent FS by using Western blot, quantitative RT-PCR, double immunofluorescence, in situ hybridization and immunoprecipitation/Western blot. After treatment of hyperthermia and the presence of induced seizures once every 2 days for 10 times, GABA(B)R1a and GABA(B)R2 subunits in hippocampus were decreased after 24 h of the last treatment. The decrease of GABABR I a lasted for 15 days but that of GABA(B)R2 persisted for more than 3 0 days. The binding of GABA(B)R1a to GABA(B)R2 in hippocampus was also decreased significantly after 24 h of the last treatment and lasted for more than 30 days. In situ hybridization showed that GABA(B)R1a mRNA was significantly decreased in dentate gyrus, and GABA(B)R2 mRNA was considerably reduced in CA(3) region. In H-10 and FS1 groups in which hyperthermia treatment was the same but no (H-10 group) or only one seizure (FS1 group) was induced, the decrease of GABA(B)R1a and GABA(B)R2 subunits and the reduced binding capability between GABA(B)R1 a and GABA(B)R2 subunits were also detected but with less severity, and the time recovering from these abnormalities was shorter. We conclude that GABA(B)R1a and GABA(B)R2 subunits and the binding of the 2 subunits decrease in hippocampus for a relatively long period of time after recurrent FS in immature rats. These changes may result in long-lasting imbalance of excitation/inhibition function in hippocampus, and are derived from the consequences of recurrent febrile seizures. (c) 2005 Elsevier Inc. All rights reserved.