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.
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.
Keywords
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Copyright
© 2009, Author(s). This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License (https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.