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Zebrafish as a novel model to assess Na+/K(+)-ATPase-related neurological disorders.

Abstract
Modeling neurological disorders using zebrafish increases rapidly as this model system allows easy access to all developmental stages and imaging of pathological processes. A surprising degree of functional conservation has been demonstrated between human genes implicated in neurodegenerative diseases and their zebrafish orthologues. Zebrafish offers rapid high throughput screening of therapeutic compounds and live imaging of pathogenic mechanisms in vivo. Several recent zebrafish studies functionally assessed the role of the sodium-potassium pump (Na(+)/K(+)-ATPase). The Na(+)/K(+)-ATPase maintains the electrochemical gradients across the plasma membrane, essential for e.g. signaling, secondary active transport, glutamate re-uptake and neuron excitability in animal cells. Na(+)/K(+)-ATPase mutations are associated with neurological disorders, where mutations in the Na(+)/K(+)-ATPase α2 and α3 isoforms cause Familial hemiplegic migraine type 2 (FHM2) and Rapid-onset dystonia-parkinsonism (RDP)/Alternating hemiplegic childhood (AHC), respectively. In zebrafish, knock-down of Na(+)/K(+)-ATPase isoforms included skeletal and heart muscle defects, impaired embryonic motility, depolarized Rohon-beard neurons and abrupt brain ventricle development. In this review, we discuss zebrafish as a model to assess Na(+)/K(+)-ATPase isoform functions. Furthermore, studies investigating proteomic changes in both α2- and α3-isoform deficient embryos and their potential connections to the Na(+)/K(+)-ATPase functions will be discussed.
AuthorsCanan Doğanli, Claus Oxvig, Karin Lykke-Hartmann
JournalNeuroscience and biobehavioral reviews (Neurosci Biobehav Rev) Vol. 37 Issue 10 Pt 2 Pg. 2774-87 (Dec 2013) ISSN: 1873-7528 [Electronic] United States
PMID24091024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2013 Elsevier Ltd. All rights reserved.
Chemical References
  • Sodium-Potassium-Exchanging ATPase
Topics
  • Animals
  • Disease Models, Animal
  • Humans
  • Migraine with Aura (diagnosis, genetics)
  • Mutation (genetics)
  • Nervous System Diseases (diagnosis, genetics)
  • Parkinson Disease (genetics)
  • Sodium-Potassium-Exchanging ATPase (genetics, metabolism)
  • Zebrafish

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