Catamenial-like Seizure Exacerbation in Mice with Targeted Ablation of Extrasynaptic Delta GABA-A Receptors in the Brain

Catamenial Epilepsy
Wednesday, November 29, 2017

Clossen BL, Reddy DS. Journal of Neuroscience Research 95(2017): 1906–1916

Purpose

  • Catamenial epilepsy is a phenomenon where seizures in women worsen during certain periods in the menstrual cycle.
  • In 2016, we presented a four-part article series summarizing catamenial epilepsy and what we know about it.
  • Neurosteroids (or “steroids made in the brain”) can affect excitability of neurons.
    • They have a role in a variety of functions, such response to stress, memory, and depression.
    • Preliminary studies have shown that neurosteroids may play a role in catamenial epilepsy.
  • Gamma amino butyric acid (GABA) is an inhibitory neurotransmitter responsible for dampening down excitability of neurons.
    • GABA acts by way of its receptors known as GABA receptors (GABARs); these receptors are made of proteins called “subunits.”
    • In neurons, these subunits come together in various combinations to form different GABAR subtypes.
    • One GABAR subtype containing the delta subunit is responsible for “tonic” (sustained) inhibition of neurons.
  • In this study, the authors looked at the effect of delta subunit-containing GABARs on catamenial epilepsy.
  • The “neurosteroid withdrawal method” is one way to simulate catamenial epilepsy in experimental animals.

Description of study

This study was done in female mice in the lab.

  • The authors used two groups of mice – normal (wildtype = WT) mice, and those that had the delta subunit of the GABAR deleted (delta knockout mice = delta KO)
  • All mice were subject to the neurosteroid withdrawal method of catamenial epilepsy that has been developed and used by other scientists previously.

Summary of study findings

  • When mice were subject to the neurosteroid withdrawal method of catamenial epilepsy, delta KO mice had a starkly different response from WT mice.
  • Delta KO mice had a higher susceptibility to seizures.
  • Delta KO mice had more seizures that lasted a longer time compared to WT mice.
  • When seizures did occur, they were more intense in delta KO than in WT mice.

What does this mean?

  • This article highlights the role of the delta subunit of GABAR subunit in catamenial epilepsy.
  • Since removal of the delta subunit of GABARs rendered mice more susceptible to seizures, the authors suggest that delta subunit containing GABARs may have a protective role in catamenial epilepsy.
  • Catamenial epilepsy is a complex phenomenon without effective treatment options.
  • The data gleaned in this study can be used to develop targeted therapies for catamenial seizures in the future.

Article published in Journal of Neuroscience Research, February 2017.

Authored by: Sloka Iyengar PhD | Basic Science Editor on 11/2017

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The mission of the Epilepsy Foundation is to lead the fight to overcome the challenges of living with epilepsy and to accelerate therapies to stop seizures, find cures, and save lives.

 
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