Alterations of the expression of RGS4 and RGS10 proteins in the anticonvulsant effects of low frequency stimulation on perforant path kindling in adult male rats

Application of low-frequency stimulation (LFS) is a new method for treatment of drug resistant epileptic patients. Previous studies demonstrated that activation of receptors coupled to Gi proteins is one of the mechanisms of the anticonvulsant effect of LFS. Thus, in this study, alterations in the expression of RGS4 and RGS10 proteins, as negative regulators of Gi proteins, were investigated.

Animals were kindled by perforant path stimulation in a rapid kindling manner (12 stimulation per day, 1 ms pulse duration at 50 Hz). LFS (8 stimulation per day, 0.1 ms pulse duration at 1 Hz, 200 pulses) was applied to the perforant path 5 minute after the termination of kindling stimulations. After electrophysiological recordings for 6 days, the dentate gyrus of the animals was removed and RGS4 and RGS10 protein expression was studied by western blotting technique.

Application of LFS significantly retarded kindling acquisition and increased the number of stimulations to achieve different stages of seizure. LFS also significantly reduced after discharge duration. In addition, application of LFS after kindling stimulation reduced the expression of RGS4 and RGS10 proteins.

Results of the present study showed that LFS has anticonvulsant effects on the perforant path kindling. Application of LFS following kindling stimulation reduced the expression of RGS4 and RGS10 proteins. Reduction of the expression of these proteins results in the longer activation of signaling pathways of Gi proteins, which may be responsible for LFS anticonvulsant effects.