Using MRI to measure in vivo free radical production and perfusion dynamics in a mouse model of elevated oxidative stress and neurogenic atrophy

Publication date: Available online 21 August 2019Source: Redox BiologyAuthor(s): Bumsoo Ahn, Nataliya Smith, Debra Saunders, Rojina Ranjit, Parker Kneis, Rheal A. Towner, Holly Van RemmenAbstractMitochondrial dysfunction, reactive oxygen species (ROS) and oxidative damage have been implicated to play a causative role in age-related skeletal muscle atrophy and weakness (i.e. sarcopenia). Mice lacking the superoxide scavenger CuZnSOD (Sod1−/−) exhibit high levels of oxygen-derived radicals and oxidative damage, associated with neuronal and muscular phenotypes consistent with sarcopenia. We used magnetic resonance imaging (MRI) technology combined with immunospin-trapping (IST) to measure in vivo free radical levels in skeletal muscle from wildtype, Sod1−/− and SynTgSod1−/− mice, a mouse model generated using targeted expression of the human Sod1 transgene specifically in neuronal tissues to determine the impact of motor neuron degeneration in muscle atrophy. By combining the spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) and molecular MRI (mMRI), we monitored the level of free radicals in mouse hindlimb muscle. The level of membrane-bound macromolecular radicals in the quadriceps muscle was elevated by ∼3-fold in Sod1−/− mice, but normalized to wildtype levels in SynTgSod1−/− rescue mice. Skeletal muscle mass was reduced by ∼25–30% in Sod1−/− mice, but fully reversed in muscle from SynTgSod1−/− mice. Using perfusion MRI we also measured the ...
Source: Redox Biology - Category: Biology Source Type: research