Related Experiment Video
Updated: Feb 2, 2026

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro
Published on: June 13, 2011
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.
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.
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.
Related Concept Videos
Spreading of Chromatin Modifications
Writers
The writer...
Freezing Point Depression and Boiling Point Elevation
The boiling point of a liquid is the temperature at which its vapor pressure is equal to ambient atmospheric pressure. Since the vapor pressure of a solution is lowered due to the presence of nonvolatile solutes, it stands to reason that the solution’s boiling point will subsequently be increased. Vapor pressure increases with temperature, and so a solution will require a higher temperature than will pure solvent to achieve any given vapor pressure, including one...
Long-term Depression
Long-term Depression
Calcium Ion Concentration Mechanism
If over...
Depressants
Alcohol is a common depressant that can induce a sense of relaxation and reduced inhibition at low doses. Contrary to its occasional...
Increasing Function

