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Hippocampal Low-Frequency Stimulation Decreased cAMP Response Element-Binding Protein and Increased GABAA Receptor Subunit α1 in Amygdala-Kindled Pharmacoresistant Epileptic Rats

Author(s): Guofeng Wu, Zhaoyang Liu, Likun Wang, Xin Zhou and Tianfu Li


Aim: To observe the changes in cAMP response element-binding protein (CREB) and GABAA receptor subunit α1 in amygdala-kindled pharmacoresistant epileptic rats subjected to hippocampal low-frequency stimulation (Hip-LFS).

Methods: A total of sixteen pharmacoresistant epileptic rats were selected from fifty rats with amygdalakindled epilepsy by testing their seizure response to phenytoin (PHT) and phenobarbital (PB). The pharmacoresistant epileptic rats were assigned to a pharmacoresistant control group (PRC group) or a pharmacoresistant stimulation group (PRS group), each of which included 8 rats. The same number of pharmacosensitive epileptic rats was assigned to a pharmacosensitive control group (PSC group, 8 rats). A normal rat control (NRC) group of 8 rats was also used in the study. A stimulation electrode was implanted in the hippocampus of each rat from each of the four groups. Hip-LFS was administered to the PRS group twice per day for 2 weeks. The other three groups only received hippocampal sham stimulation. Following 2 weeks of Hip- LFS, seizure degree and amygdala EEG were recorded. The levels of CREB protein and GABAA receptor subunit α1 in the hippocampal tissues were measured by a Western blot.

Results:The CREB level increased remarkably and the GABAA receptor subunit α1 level decreased in the pharmacoresistant epileptic rats compared with the control. Following two weeks of Hip-LFS, stimulation-induced seizures and amygdala EEG were inhibited significantly. The CREB and p-CREB level decreased significantly in the PRS group compared with the PRC group. However, the GABAA α1 subunit level in the PRS group increased dramatically compared with that in the PRC group.

Conclusions: Hip-LFS might increase the expression of the GABAA α1 subunit and decrease the level of CREB. The Hip-LFS-induced increase in the level of the GABAA receptor α1 subunit might be associated with the decreases in CREB and p-CREB in the treatment of amygdala-kindled pharmacoresistant epileptic rats.


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