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  • Bottger, P (author)

Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-02-25
  • Springer Science and Business Media LLC,2016

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:133021582
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:133021582URI
  • https://doi.org/10.1038/srep22047DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 ...)

  • Glerup, S (author)
  • Gesslein, B (author)
  • Illarionova, NB (author)
  • Isaksen, TJ (author)
  • Heuck, A (author)
  • Clausen, BH (author)
  • Fuchtbauer, EM (author)
  • Gramsbergen, JB (author)
  • Gunnarson, EKarolinska Institutet (author)
  • Aperia, AKarolinska Institutet (author)
  • Lauritzen, M (author)
  • Lambertsen, KL (author)
  • Nissen, P (author)
  • Lykke-Hartmann, K (author)
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Scientific reports: Springer Science and Business Media LLC6, s. 22047-2045-2322

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