Schweizer, U.* ; Wirth, E.K.* ; Klopstock, T.* ; Hölter, S.M. ; Becker, L. ; Moskovitz, J.* ; Grune, T.* ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Köhrle, J.* ; Schomburg, L.*
Seizures, ataxia and parvalbumin-expressing interneurons respond to selenium supply in Selenop-deficient mice.
Redox Biol. 57:102490 (2022)
Mice with constitutive disruption of the Selenop gene have been key to delineate the importance of selenoproteins in neurobiology. However, the phenotype of this mouse model is exquisitely dependent on selenium supply and timing of selenium supplementation. Combining biochemical, histological, and behavioral methods, we tested the hypothesis that parvalbumin-expressing interneurons in the primary somatosensory cortex and hippocampus depend on dietary selenium availability in Selenop-/- mice. Selenop-deficient mice kept on adequate selenium diet (0.15 mg/kg, i.e. the recommended dietary allowance, RDA) developed ataxia, tremor, and hyperexcitability between the age of 4-5 weeks. Video-electroencephalography demonstrated epileptic seizures in Selenop-/- mice fed the RDA diet, while Selenop± heterozygous mice behaved normally. Both neurological phenotypes, hyperexcitability/seizures and ataxia/dystonia were successfully prevented by selenium supplementation from birth or transgenic expression of human SELENOP under a hepatocyte-specific promoter. Selenium supplementation with 10 μM selenite in the drinking water on top of the RDA diet increased the activity of glutathione peroxidase in the brains of Selenop-/- mice to control levels. The effects of selenium supplementation on the neurological phenotypes were dose- and time-dependent. Selenium supplementation after weaning was apparently too late to prevent ataxia/dystonia, while selenium withdrawal from rescued Selenop-/- mice eventually resulted in ataxia. We conclude that SELENOP expression is essential for preserving interneuron survival under limiting Se supply, while SELENOP appears dispensable under sufficiently high Se status.
Impact Factor
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Times Cited
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Brain ; Dystonia ; Epilepsy ; Pvalb ; Selenoprotein
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2022
Prepublished im Jahr
HGF-Berichtsjahr
2022
ISSN (print) / ISBN
2213-2317
e-ISSN
2213-2317
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 57,
Heft: ,
Seiten: ,
Artikelnummer: 102490
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
Amsterdam [u.a.]
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30204 - Cell Programming and Repair
30201 - Metabolic Health
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-500500-001
G-500692-001
G-500600-001
Förderungen
Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
Copyright
Erfassungsdatum
2022-10-19