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ERK activation is required for the antiepileptogenic effect of low frequency electrical stimulation in kindled rats

Parastoo Mardani1, Shahrbanoo Oryan1, Abdolrahman Sarihi2

  • 1Department of Biology, Faculty of Sciences, Kharazmi University, Tehran, Iran.

Brain Research Bulletin
|April 30, 2018
PubMed
Abstract

Insights

Low frequency electrical stimulation (LFS) reduces kindled seizures by activating the extracellular signal-regulated kinase (ERK) pathway. Inhibiting ERK partially blocks LFS

Area of Science:

  • Neuroscience
  • Epilepsy Research
  • Signal Transduction

Background:

  • The precise molecular mechanisms underlying the antiepileptogenic effects of low frequency electrical stimulation (LFS) remain incompletely understood.
  • Investigating the role of specific signaling cascades, such as the extracellular signal-regulated kinase (ERK) pathway, is crucial for elucidating LFS's therapeutic potential in epilepsy.

Purpose of the Study:

  • To determine the involvement of the extracellular signal-regulated kinase (ERK) signaling cascade in mediating the inhibitory effects of low frequency electrical stimulation (LFS) on kindled seizures.
  • To explore the impact of ERK inhibition on LFS-induced modulation of seizure parameters and neuronal excitability in a rodent model of epilepsy.

Main Methods:

  • A semi-rapid perforant path kindling protocol was employed in animals over seven days.
  • Low frequency electrical stimulation (LFS) was applied daily post-kindling stimulation.
  • FR180204, an ERK inhibitor, was intracerebroventricularly microinjected before LFS, and p-ERK expression in the dentate gyrus was assessed via immunohistochemistry.

Main Results:

  • Low frequency electrical stimulation (LFS) demonstrated an inhibitory effect on the kindling rate.
  • Microinjection of FR180204 prior to LFS attenuated the inhibitory effects of LFS on seizure severity and field potential parameters.
  • LFS application increased the expression of phosphorylated ERK (p-ERK) in the dentate gyrus, and FR180204 blocked LFS's effects on paired-pulse depression.

Conclusions:

  • The extracellular signal-regulated kinase (ERK) signaling pathway plays a significant role in mediating the antiepileptogenic effect of low frequency electrical stimulation (LFS) in perforant path kindling.
  • These findings offer valuable insights into the mechanisms of LFS in epilepsy therapy and suggest potential therapeutic targets.
Keywords:
Brain stimulationDentate gyrusERK signalingEpilepsy

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