| First Author | Qi Y | Year | 2015 |
| Journal | Front Aging Neurosci | Volume | 7 |
| Pages | 204 | PubMed ID | 26539112 |
| Mgi Jnum | J:288688 | Mgi Id | MGI:6433182 |
| Doi | 10.3389/fnagi.2015.00204 | Citation | Qi Y, et al. (2015) PGC-1alpha Silencing Compounds the Perturbation of Mitochondrial Function Caused by Mutant SOD1 in Skeletal Muscle of ALS Mouse Model. Front Aging Neurosci 7:204 |
| abstractText | Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease causing death of motor neurons. This study investigated the roles of energy metabolism in the pathogenesis of ALS in the SOD1(G93A) transgenic mouse model. Control and SOD1(G93A) mice were administered with shcontrol or shPGC-1alpha in combination with PBS or thiazolidinedione (TZD) for 8 weeks. Gene expression was analyzed by quantitative real-time PCR and Western blot. ROS and fibrosis were assessed with a colorimetric kit and Sirius staining, respectively. Inflammatory cytokines were measured using ELISA kits. The levels of tissue ROS and serum inflammatory cytokines were significantly higher in SOD1(G93A) mice compared to control mice, and knocking down peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) drastically increased cytokine levels in both control and SOD1(G93A) mice. Muscle fibrosis was much severer in SOD1(G93A) mice, and worsened by silencing PGC-1alpha and attenuated by TZD. The expression levels of PGC-1alpha, SOD1, UCP2, and cytochrome C were substantially reduced by shPGC-1alpha and increased by TZD in muscle of both control and SOD1(G93A) mice, whereas the level of NF-kappaB was significantly elevated in SOD1(G93A) mice, which was further increased by PGC-1alpha silencing. These data indicated that disruption of energy homeostasis would exacerbate the pathological changes caused by SOD1 mutations to promote the pathogenesis of ALS. |
