Melissa Bowerman m.bowerman@keele.ac.uk
KCC3 loss-of-function contributes to Andermann syndrome by inducing activity-dependent neuromuscular junction defects.
Bowerman, M; Salsac, C; Bernard, V; Soulard, C; Dionne, A; Coque, E; Benlefki, S; Hince, P; Dion, PA; Butler-Browne, G; Camu, W; Bouchard, J-P; Delpire, E; Rouleau, GA; Raoul, C; Scamps, F
Authors
C Salsac
V Bernard
C Soulard
A Dionne
E Coque
S Benlefki
P Hince
PA Dion
G Butler-Browne
W Camu
J-P Bouchard
E Delpire
GA Rouleau
C Raoul
F Scamps
Abstract
Loss-of-function mutations in the potassium-chloride cotransporter KCC3 lead to Andermann syndrome, a severe sensorimotor neuropathy characterized by areflexia, amyotrophy and locomotor abnormalities. The molecular events responsible for axonal loss remain poorly understood. Here, we establish that global or neuron-specific KCC3 loss-of-function in mice leads to early neuromuscular junction (NMJ) abnormalities and muscular atrophy that are consistent with the pre-synaptic neurotransmission defects observed in patients. KCC3 depletion does not modify chloride handling, but promotes an abnormal electrical activity among primary motoneurons and mislocalization of Na(+)/K(+)-ATPase a1 in spinal cord motoneurons. Moreover, the activity-targeting drug carbamazepine restores Na(+)/K(+)-ATPase a1 localization and reduces NMJ denervation in Slc12a6(-/-) mice. We here propose that abnormal motoneuron electrical activity contributes to the peripheral neuropathy observed in Andermann syndrome.
Journal Article Type | Article |
---|---|
Acceptance Date | Jun 20, 2017 |
Online Publication Date | Jun 21, 2017 |
Publication Date | 2017-10 |
Publicly Available Date | May 26, 2023 |
Journal | Neurobiology of Disease |
Print ISSN | 0969-9961 |
Electronic ISSN | 0969-9961 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 106 |
Pages | 35 - 48 |
DOI | https://doi.org/10.1016/j.nbd.2017.06.013 |
Keywords | Motoneuron; Andermann syndrome; Chloride homeostasis; Electrical activity; Neuromuscular junction; Na+/K+ ATPase |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S0969996117301407?via%3Dihub |
Files
NBD-17-173R1-1.pdf
(1.8 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
You might also like
Downloadable Citations
About Keele Repository
Administrator e-mail: research.openaccess@keele.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search