| First Author | Dang C | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 12 | Pages | 14811-14824 |
| PubMed ID | 31718280 | Mgi Jnum | J:294758 |
| Mgi Id | MGI:6451338 | Doi | 10.1096/fj.201901149RR |
| Citation | Dang C, et al. (2019) Up-regulation of PGC-1alpha in neurons protects against experimental autoimmune encephalomyelitis. FASEB J 33(12):14811-14824 |
| abstractText | Reactive oxygen species (ROS) generation and mitochondrial dysfunction are related to neuron loss in multiple sclerosis (MS). Although peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) appears to play a key role in modulating levels of mitochondrial ROS, antioxidants, and uncoupling proteins (UCPs), and PGC-1alpha expression is reduced in the neocortex of patients with MS, it is unclear what its role is in neurons and in the manifestation of clinical symptoms of MS. Here, we show in wild-type (WT) experimental autoimmune encephalomyelitis (EAE) mice that PGC-1alpha is decreased 13 d after EAE induction followed by a steady decline up to 20 d. These changes were accompanied by parallel alterations in levels of superoxide dismutase 2, peroxiredoxin 3, thioredoxin 2, UCP4, and UCP5. In transgenic (TG) mice with neuron-specific overexpression of PGC-1alpha (PGC-1alpha(f/f)Eno2-Cre), clinical symptoms after EAE induction were delayed and less severe than in WT mice. The degrees of apoptotic neuron loss and demyelination were also less severe in PGC-1alpha-TG mice. Overexpression of PGC-1alpha in neuronal neuroblastoma spinal cord 34 cells subjected to EAE inflammatory conditions showed similar results to those obtained in vivo. RNA sequencing analysis showed that apoptotic processes were significantly enriched in the top 10 significant gene ontology (GO) terms of differentially expressed genes, and the apoptotic pathway was significantly enriched in Kyoto Encyclopedia of Genes and Genomes pathway analysis. Our findings indicate that up-regulation of neuronal PGC-1alpha protected neurons from apoptosis in EAE. Manipulating PGC-1alpha levels in MS may help stave off this devastating disease.-Dang, C., Han, B., Li, Q., Han, R., Hao, J. Up-regulation of PGC-1alpha in neurons protects against experimental autoimmune encephalomyelitis. |
