| First Author | Kros L | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 16959 |
| PubMed ID | 30446731 | Mgi Jnum | J:268717 |
| Mgi Id | MGI:6271813 | Doi | 10.1038/s41598-018-35285-8 |
| Citation | Kros L, et al. (2018) Increased susceptibility to cortical spreading depression and epileptiform activity in a mouse model for FHM2. Sci Rep 8(1):16959 |
| abstractText | 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 alpha2 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 alpha2 isoform, we set to unravel whether alpha2(+/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, alpha2(+/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, alpha2(+/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. |
