Increased susceptibility to cortical spreading depression and epileptiform activity in a mouse model for FHM2

Lieke Kros1,2, Karin Lykke-Hartmann3,4, Kamran Khodakhah5

  • 1Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY, 10461, USA. l.kros@erasmusmc.nl.

Scientific Reports
|November 18, 2018
PubMed

Insights

Familial hemiplegic migraine type 2 (FHM2) mice with a specific ATP1A2 mutation showed increased susceptibility to cortical spreading depression and epilepsy. This mouse model aids understanding of migraine comorbidities and potential treatments.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Migraine is a common, disabling neurological disorder.
  • Familial hemiplegic migraine type 2 (FHM2) is a rare subtype caused by ATP1A2 gene mutations, affecting astrocytic Na+/K+-ATPase.
  • FHM2 patients often exhibit comorbidities like epilepsy and psychiatric disorders.

Purpose of the Study:

  • To investigate epilepsy and cortical spreading depression (CSD) susceptibility in a mouse model of FHM2.
  • To analyze the impact of the G301R mutation in the α2 isoform of Na+/K+-ATPase on neurological activity.
  • To explore potential age- and sex-related differences in FHM2 pathophysiology.

Main Methods:

  • Utilized a mouse model with the G301R disease-mutation in the α2 Na+/K+-ATPase isoform.
  • Performed in vivo experiments involving cortical KCl application in adult and aged male and female mice.
  • Recorded and analyzed cortical spreading depression (CSD) and epileptiform activity.

Main Results:

  • Mice with the α2+/G301R mutation exhibited heightened susceptibility to both CSD and epileptiform activity.
  • Epileptiform activity was observed to be superimposed on CSD events.
  • Age-related alterations in CSD susceptibility suggested a role for female sex hormones in migraine pathophysiology.

Conclusions:

  • The α2+/G301R mouse model effectively replicates key FHM2 symptoms, including epilepsy and CSD.
  • This model is valuable for studying the pathophysiology of generalized epilepsy and its comorbidity with migraine.
  • The model offers potential for developing and testing future migraine treatment strategies.

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