| First Author | Agudelo LZ | Year | 2014 |
| Journal | Cell | Volume | 159 |
| Issue | 1 | Pages | 33-45 |
| PubMed ID | 25259918 | Mgi Jnum | J:213551 |
| Mgi Id | MGI:5585268 | Doi | 10.1016/j.cell.2014.07.051 |
| Citation | Agudelo LZ, et al. (2014) Skeletal Muscle PGC-1alpha1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression. Cell 159(1):33-45 |
| abstractText | Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which skeletal muscle PGC-1alpha1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1alpha1-PPARalpha/delta pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1alpha1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration. This study opens therapeutic avenues for the treatment of depression by targeting the PGC-1alpha1-PPAR axis in skeletal muscle, without the need to cross the blood-brain barrier. |
