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Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model
- Bottger, P (author)
- Glerup, S (author)
- Gesslein, B (author)
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- Illarionova, NB (author)
- Isaksen, TJ (author)
- Heuck, A (author)
- Clausen, BH (author)
- Fuchtbauer, EM (author)
- Gramsbergen, JB (author)
- Lauritzen, M (author)
- Lambertsen, KL (author)
- Nissen, P (author)
- Lykke-Hartmann, K (author)
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- (creator_code:org_t)
- 2016-02-25
- 2016
- English.
- In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 22047-
- Journal article (peer-reviewed)
Abstract
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- Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments and psychiatric manifestations, such as obsessive-compulsive disorder (OCD). FHM2 disease-mutations locate to the ATP1A2 gene encoding the astrocyte-located α2-isoform of the sodium-potassium pump (α2Na+/K+-ATPase). We show that knock-in mice heterozygous for the FHM2-associated G301R-mutation (α2+/G301R) phenocopy several FHM2-relevant disease traits e.g., by mimicking mood depression and OCD. In vitro studies showed impaired glutamate uptake in hippocampal mixed astrocyte-neuron cultures from α2G301R/G301R E17 embryonic mice, and moreover, induction of cortical spreading depression (CSD) resulted in reduced recovery in α2+/G301R male mice. Moreover, NMDA-type glutamate receptor antagonists or progestin-only treatment reverted specific α2+/G301R behavioral phenotypes. Our findings demonstrate that studies of an in vivo relevant FHM2 disease knock-in mouse model provide a link between the female sex hormone cycle and the glutamate system and a link to co-morbid psychiatric manifestations of FHM2.
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- Bottger, P
- Glerup, S
- Gesslein, B
- Illarionova, NB
- Isaksen, TJ
- Heuck, A
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- Clausen, BH
- Fuchtbauer, EM
- Gramsbergen, JB
- Gunnarson, E
- Aperia, A
- Lauritzen, M
- Lambertsen, KL
- Nissen, P
- Lykke-Hartmann, ...
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- Karolinska Institutet
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