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Glutamate-system de...
Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model
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Bottger, P (författare)
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Glerup, S (författare)
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Gesslein, B (författare)
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visa fler...
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Illarionova, NB (författare)
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Isaksen, TJ (författare)
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Heuck, A (författare)
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Clausen, BH (författare)
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Fuchtbauer, EM (författare)
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Gramsbergen, JB (författare)
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- Gunnarson, E (författare)
- Karolinska Institutet
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- Aperia, A (författare)
- Karolinska Institutet
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Lauritzen, M (författare)
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Lambertsen, KL (författare)
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Nissen, P (författare)
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Lykke-Hartmann, K (författare)
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(creator_code:org_t)
- 2016-02-25
- 2016
- Engelska.
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 22047-
- Relaterad länk:
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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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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- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Bottger, P
-
Glerup, S
-
Gesslein, B
-
Illarionova, NB
-
Isaksen, TJ
-
Heuck, A
-
visa fler...
-
Clausen, BH
-
Fuchtbauer, EM
-
Gramsbergen, JB
-
Gunnarson, E
-
Aperia, A
-
Lauritzen, M
-
Lambertsen, KL
-
Nissen, P
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Lykke-Hartmann, ...
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visa färre...
- Artiklar i publikationen
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Scientific repor ...
- Av lärosätet
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Karolinska Institutet