Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice.

Details

Serval ID
serval:BIB_FC3AF9A33638
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice.
Journal
Neurobiology of Disease
Author(s)
Bernard-Marissal N., Sunyach C., Marissal T., Raoul C., Pettmann B.
ISSN
1095-953X (Electronic)
ISSN-L
0969-9961
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
73
Pages
130-136
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Although the precise signaling mechanisms underlying the vulnerability of some sub-populations of motoneurons in ALS remain unclear, critical factors such as metallo-proteinase 9 expression, neuronal activity and endoplasmic reticulum stress have been shown to be involved. In the context of SOD1(G93A) ALS mouse model, we previously showed that a two-fold decrease in calreticulin (CRT) is occurring in the vulnerable fast motoneurons. Here, we asked to which extent the decrease in CRT levels was causative to muscle denervation and/or motoneuron degeneration. Toward this goal, a hemizygous deletion of the crt gene in SOD1(G93A) mice was generated since the complete ablation of crt is embryonic lethal. We observed that SOD1(G93A);crt(+/-) mice display increased and earlier muscle weakness and muscle denervation compared to SOD1(G93A) mice. While CRT reduction in motoneurons leads to a strong upregulation of two factors important in motoneuron dysfunction, ER stress and mTOR activation, it does not aggravate motoneuron death. Our results underline a prevalent role for CRT levels in the early phase of muscle denervation and support CRT regulation as a potential therapeutic approach.
Pubmed
Web of science
Create date
17/01/2015 11:04
Last modification date
20/08/2019 16:27
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