Constitutive PGC-1 α Overexpression in Skeletal Muscle Does Not Improve Morphological Outcome in Mouse Models of Brain Irradiation or Cortical Stroke

Publication date: 1 August 2018 Source:Neuroscience, Volume 384 Author(s): Lars Karlsson, María Nazareth González-Alvarado, Mar Larrosa-Flor, Ahmed Osman, Mats Börjesson, Klas Blomgren, Hans Georg Kuhn Physical exercise can improve morphological outcomes after ischemic stroke and ameliorate irradiation-induced reduction of hippocampal neurogenesis in rodents, but the mechanisms underlying these effects remain largely unknown. The transcription factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is considered to be one of the central factors responsible for exercise-induced benefits in skeletal muscle, including the release of neurotrophic factors into the circulation. In order to test if PGC-1α overexpression in skeletal muscle could simulate the exercise-induced effects on recovery after cranial irradiation and stroke, we used male adult transgenic mice overexpressing murine PGC-1α under the control of muscle creatinine kinase promoter and subjected them to either whole brain irradiation at a dose of 4 Gy or photothrombotic stroke to the sensory motor cortex. Muscular PGC-1α overexpression did not ameliorate irradiation-induced reduction of newborn BrdU-labeled cells in the dentate gyrus, immature neurons, or newborn mature neurons. In the stroke model, muscular overexpression of PGC-1α resulted in an increased infarct size without any changes in microglia activation or reactive astrocytosis. No difference could be detected...
Source: Neuroscience - Category: Neuroscience Source Type: research