| First Author | Bernard-Marissal N | Year | 2015 |
| Journal | Neurobiol Dis | Volume | 73 |
| Pages | 130-6 | PubMed ID | 25277755 |
| Mgi Jnum | J:218446 | Mgi Id | MGI:5617630 |
| Doi | 10.1016/j.nbd.2014.09.009 | Citation | Bernard-Marissal N, et al. (2015) Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice. Neurobiol Dis 73:130-6 |
| abstractText | 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. |
