Regression of Epileptogenesis by Inhibiting Tropomyosin Kinase B Signaling following a Seizure

Kamesh Krishnamurthy1, Yang Zhong Huang1, Stephen C Harward2

  • 1Department of Neurobiology, Duke University, Durham, NC.

Annals of Neurology
|September 17, 2019
PubMed
Abstract

Insights

Transiently inhibiting tropomyosin kinase B (TrkB)-phospholipase-C-gamma-1 (PLCγ1) signaling after a seizure can limit epilepsy progression. This approach may offer a new strategy for treating temporal lobe epilepsy (TLE).

Area of Science:

  • Neuroscience
  • Epilepsy Research
  • Molecular Signaling

Background:

  • Temporal lobe epilepsy (TLE) is a neurological disorder characterized by recurrent seizures.
  • Approximately 35% of TLE patients experience persistent seizures despite medication.
  • Seizures themselves may contribute to epilepsy progression, a process known as epileptogenesis.

Purpose of the Study:

  • To investigate the role of tropomyosin kinase B (TrkB)-phospholipase-C-gamma-1 (PLCγ1) signaling in seizure-induced epileptogenesis.
  • To determine if inhibiting TrkB-PLCγ1 signaling after a seizure can prevent or reverse epilepsy progression.

Main Methods:

  • A modified kindling model was used, inducing an isolated seizure via amygdala stimulation.
  • TrkB-PLCγ1 signaling was transiently inhibited for two days post-seizure using chemical-genetic or pharmacologic methods.
  • Seizure severity and duration were assessed using behavioral and electrographic measures.

Main Results:

  • Transient inhibition of TrkB-PLCγ1 signaling post-seizure reduced the severity and duration of subsequent seizures.
  • This inhibition also appeared to revert some animals to an earlier stage of epileptogenesis.
  • Inhibition of TrkB-PLCγ1 signaling without a recent seizure did not affect seizure severity.

Conclusions:

  • Transient inhibition of TrkB-PLCγ1 signaling following a seizure represents a potential therapeutic strategy for TLE.
  • This approach may limit epilepsy progression and ameliorate seizure severity.
  • Targeting TrkB-PLCγ1 signaling offers a novel avenue for TLE treatment.

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