Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pumpReportar como inadecuado




Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Reference: Isaksen, TJ, Kros, L, Vedovato, N et al., (2017). Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump. PLoS Genetics, 13 (5), e1006763.Citable link to this page:

 

Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump

Abstract: Mutations in the neuron-specific α3 isoform of the Na+/K+-ATPase are found in patients suffering from Rapid onset Dystonia Parkinsonism and Alternating Hemiplegia of Childhood, two closely related movement disorders. We show that mice harboring a heterozygous hot spot disease mutation, D801Y (α3+/D801Y), suffer abrupt hypothermia-induced dystonia identified by electromyographic recordings. Single-neuron in vivo recordings in awake α3+/D801Y mice revealed irregular firing of Purkinje cells and their synaptic targets, the deep cerebellar nuclei neurons, which was further exacerbated during dystonia and evolved into abnormal high-frequency burst-like firing. Biophysically, we show that the D-to-Y mutation abolished pump-mediated Na+/K+ exchange, but allowed the pumps to bind Na+ and become phosphorylated. These findings implicate aberrant cerebellar activity in α3 isoform-related dystonia and add to the functional understanding of the scarce and severe mutations in the α3 isoform Na+/K+-ATPase.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2017-04-17Notes:This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website: https://www.plos.org/

Journal: PLoS Geneticssee more from them

Publication Website: http://journals.plos.org/plosgenetics/

Volume: 13

Issue: 5

Issue Date: 2017-05-04

pages:e1006763Identifiers

Doi: https://doi.org/10.1371/journal.pgen.1006763

Issn: 1553-7390

Eissn: 1553-7404

Uuid: uuid:1918a537-4c29-405b-ab76-cba33f420bb8

Urn: uri:1918a537-4c29-405b-ab76-cba33f420bb8

Pubs-id: pubs:692287 Item Description

Type: journal-article;

Version: Publisher's version

Relationships





Autor: Isaksen, TJ - fundingDanish National Research Foundation grantNumberDNRF85 fundingAarhus University - - - Kros, L - - - Vedovato,

Fuente: https://ora.ox.ac.uk/objects/uuid:1918a537-4c29-405b-ab76-cba33f420bb8



DESCARGAR PDF




Documentos relacionados