The role of serine/threonine protein phosphatases in the inhibitory effects of low frequency stimulasion in perforant path kindled seizures acquisition

Abstract

Background: The use of low-frequency electrical stimulation (LFS) as a therapy for epilepsy is currently being studied in experimental animals and patients with epilepsy. In the present study, we investigated the role of serine/threonine protein phosphatases in the inhibitory effects of LFS on perforant path kindling acquisition. Materials and Methods: Sixty four male Wistar rats were stimulated by perforant path stimulation in a rapid kindling manner (6 stimulations per day). The LFS (1 Hz) was applied immediately after termination of each kindling stimulation. The FK506 (1μM; i.c.v.), a serine/threonine protein phosphatase PP2B inhibitor and okadaic acid (1μM;i.c.v.), a serine/threonine protein phosphatases PP1/2A inhibitor, were daily microinjected into the left ventricle 10 min before starting the stimulation protocol. A two-way ANOVA was done to compare the seizure parameters of different groups. The effect of LFS on behavioral seizure scores was analyzed using the nonparametric Kruskal Wallis and Mann Whitney U tests. P value less than 0.05 was considered as the level of significance. Results: Appling LFS immediately after kindling stimulation significantly retarded the kindling acquisition and delayed the expression of different kindled seizure stages. In addition, LFS significantly reduced the increment of daily after-discharge duration during kindling development. Microinjection of neither FK506 nor okadaic acid had significant effect on the antiepileptogenic effect of LFS on kindling parameters. Conclusion: Our findings showed that activation of PP1/2A and PP2B, which play a critical role in LFS, induced down-regulation of synaptic strength, had no role in mediating the inhibitory effects of LFS on perforant path kindled seizures.