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

Lieke Kros, Karin Lykke-Hartmann, Kamran Khodakhah

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Migraine is a highly prevalent, debilitating, episodic headache disorder affecting roughly 15% of the population. Familial hemiplegic migraine type 2 (FHM2) is a rare subtype of migraine caused by mutations in the ATP1A2 gene, encoding the α2 isoform of the Na+/K+-ATPase, predominantly expressed in astrocytes. Differential comorbidities such as epilepsy and psychiatric disorders manifest in patients. Using a mouse model harboring the G301R disease-mutation in the α2 isoform, we set to unravel whether α2 +/G301R mice show an increased susceptibility for epilepsy and cortical spreading depression (CSD). We performed in vivo experiments involving cortical application of KCl in awake head-restrained male and female mice of different age groups (adult and aged). Interestingly, α2 +/G301R mice indeed showed an increased susceptibility to both CSD and epileptiform activity, closely replicating symptoms in FHM2 patients harboring the G301R and other FHM2-causing mutations. Additionally, this epileptiform activity was superimposed on CSDs. The age-related alteration towards CSD indicates the influence of female sex hormones on migraine pathophysiology. Therefore, the FHM2, α2 +/G301R mouse model can be utilized to broaden our understanding of generalized epilepsy and comorbidity hereof in migraine, and may be utilized toward future selection of possible treatment options for migraine.

Original languageEnglish (US)
Article number16959
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Cortical Spreading Depression
Migraine Disorders
Mutation
Comorbidity
Epilepsy
Protein Isoforms
Generalized Epilepsy
Headache Disorders
Gonadal Steroid Hormones
Astrocytes
Psychiatry
Age Groups
Head
Familial type 2 Hemiplegic migraine
Population
Genes

ASJC Scopus subject areas

  • General

Cite this

Increased susceptibility to cortical spreading depression and epileptiform activity in a mouse model for FHM2. / Kros, Lieke; Lykke-Hartmann, Karin; Khodakhah, Kamran.

In: Scientific Reports, Vol. 8, No. 1, 16959, 01.12.2018.

Research output: Contribution to journalArticle

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