Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity

Glial support is critical for normal axon function and can become dysregulated in white matter (WM) disease. In humans, loss-of-function mutations of which encodes the inward-rectifying potassium channel KIR4.1, causes seizures and progressive neurological decline. We investigated Kir4.1 functions i...

Full description

Saved in:

Bibliographic Details
Published in:	eLife Vol. 7
Main Authors:	Schirmer, Lucas, Möbius, Wiebke, Zhao, Chao, Cruz-Herranz, Andrés, Ben Haim, Lucile, Cordano, Christian, Shiow, Lawrence R, Kelley, Kevin W, Sadowski, Boguslawa, Timmons, Garrett, Pröbstel, Anne-Katrin, Wright, Jackie N, Sin, Jung Hyung, Devereux, Michael, Morrison, Daniel E, Chang, Sandra M, Sabeur, Khalida, Green, Ari J, Nave, Klaus-Armin, Franklin, Robin Jm, Rowitch, David H
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 11-09-2018 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	Age Animals Axons - metabolism Axons - pathology Cloning Humans Immunoglobulins Kir4.1 (KCNJ10) Leukoencephalopathies - genetics Leukoencephalopathies - physiopathology Mice Mice, Knockout Mitochondria Myelin neurobiology Neurodegeneration Neuroglia - metabolism Neuroglia - pathology Neurons Neurons - metabolism Neurons - pathology Neuroscience Neurosciences Oligodendrocytes Oligodendroglia - metabolism Oligodendroglia - pathology Potassium Potassium channels Potassium channels (inwardly-rectifying) Potassium Channels, Inwardly Rectifying - genetics Proteins Retina Seizures Seizures (Medicine) Seizures - genetics Seizures - physiopathology Software Spinal Cord - metabolism Spinal Cord - physiopathology Spinal cord injuries Stem cells Substantia alba Visual evoked potentials visual System white matter San Francisco California California United Kingdom > UK United States > US Germany mouse white matter neuroscience neurobiology neurodegeneration oligodendrocytes visual System Kir4.1 (KCNJ10)
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Glial support is critical for normal axon function and can become dysregulated in white matter (WM) disease. In humans, loss-of-function mutations of which encodes the inward-rectifying potassium channel KIR4.1, causes seizures and progressive neurological decline. We investigated Kir4.1 functions in oligodendrocytes (OLs) during development, adulthood and after WM injury. We observed that Kir4.1 channels localized to perinodal areas and the inner myelin tongue, suggesting roles in juxta-axonal K removal. Conditional knockout (cKO) of OL- resulted in late onset mitochondrial damage and axonal degeneration. This was accompanied by neuronal loss and neuro-axonal dysfunction in adult OL- cKO mice as shown by delayed visual evoked potentials, inner retinal thinning and progressive motor deficits. Axon pathologies in OL- cKO were exacerbated after WM injury in the spinal cord. Our findings point towards a critical role of OL-Kir4.1 for long-term maintenance of axonal function and integrity during adulthood and after WM injury.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2050-084X 2050-084X
DOI:	10.7554/elife.36428