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Glutamate-system de...
Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-02-25
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Springer Science and Business Media LLC,2016
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:133021582
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http://kipublications.ki.se/Default.aspx?queryparsed=id:133021582URI
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https://doi.org/10.1038/srep22047DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
Added entries (persons, corporate bodies, meetings, titles ...)
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Glerup, S
(author)
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Gesslein, B
(author)
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Illarionova, NB
(author)
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Isaksen, TJ
(author)
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Heuck, A
(author)
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Clausen, BH
(author)
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Fuchtbauer, EM
(author)
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Gramsbergen, JB
(author)
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Gunnarson, EKarolinska Institutet
(author)
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Aperia, AKarolinska Institutet
(author)
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Lauritzen, M
(author)
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Lambertsen, KL
(author)
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Nissen, P
(author)
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Lykke-Hartmann, K
(author)
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Karolinska Institutet
(creator_code:org_t)
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In:Scientific reports: Springer Science and Business Media LLC6, s. 22047-2045-2322
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Bottger, P
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Glerup, S
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Gesslein, B
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Illarionova, NB
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Isaksen, TJ
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Heuck, A
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Clausen, BH
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Fuchtbauer, EM
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Gramsbergen, JB
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Gunnarson, E
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Aperia, A
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Lauritzen, M
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Lambertsen, KL
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Nissen, P
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Lykke-Hartmann, ...
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Karolinska Institutet