Successive alterations of hippocampal gamma-aminobutyric acid B receptor subunits in a rat model of febrile seizure.
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 GABA(B)R1a lasted for 15 days but that of GABA(B)R2 persisted for more than 30 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 CA3 region. In H10 and FS1 groups in which hyperthermia treatment was the same but no (H10 group) or only one seizure (FS(1) group) was induced, the decrease of GABA(B)R1a and GABA(B)R2 subunits and the reduced binding capability between GABA(B)R1a 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.
Han
Ying
Y
Department of Pediatrics, Peking University First Hospital, No. 1, Xi'anmen Dajie, Beijing, 100034, PR China.
Qin
Jiong
J
Bu
Ding-Fang
DF
Chang
Xing-Zhi
XZ
Yang
Zhi-Xian
ZX
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D003294:Seizures, Febrile / Q000378:metabolism*
C116566:Gabbr2 protein, rat; D021122:Protein Subunits; D018080:Receptors, GABA-B