Effects of hippocampal stimulus on α₅ subunit of extrasynaptic GABA(A) receptor in kainic acid-induced epileptic rats

Abstract

To observe the effects of electrical hippocampal stimulation of α₅ subunit of extrasynaptic GABA(A) receptor in kainic acid-induced epileptic rats, explore the optimal therapeutic parameters and elucidate the possible mechanism of electrical stimulation for hippocampal epilepsy. A total of 40 healthy male Sprague Dawley (SD) rats were randomly divided into 5 groups of epilepsy, sham operation, low-frequency stimulation (LFS), high-frequency stimulation (HFS) and normal control (n = 8 each). The expression of α₅ subunit of extrasynaptic GABA(A) receptor as well as the association with the curative effects of LFS were evaluated by behavioristics, real-time fluorogenic quantitative polymerase chain reaction (PCR) and Western blot. The kainic acid kindling rats had class V attack with a modeling success rate of 67%. After treatment, as compared with sham operation and epilepsy groups, the number of seizures decreased significantly in LFS and HFS treatment groups (P < 0.01). But LFS and HFS treatment groups were compared, the number of seizures has no statistical significance (P > 0.05). When sham operation and epilepsy groups were compared, the number of seizures was not statistically significant (P > 0.05). The paired inter-group comparisons showed that LFS and HFS treatment groups and sham operation and epilepsy groups had significant differences in α₅ subunit mRNA and protein (P < 0.01). No statistical significance existed between LFS and HFS treatment groups (P > 0.05) or sham operation and HFS treatment groups (P > 0.05). As compared with normal control group, LFS treatment and HFS groups had significant difference (P < 0.01). Electrical hippocampal stimulation can effectively inhibit seizures. Both LFS and HFS are equally effective, but the former offers greater benefits. And an inhibition of extrasynaptic α₅ subunit plays an important role in seizure during hippocampal stimulation.