Increased skeletal muscle akt content in a murine model of motor neuron disease

Potential alterations in the skeletal muscle P13-WAkt pathway were examined in a murine model of ALS, due to its documented role in maintaining muscle mass andlor ameliorating apoptosis. Hindlimb muscle from G93A mice was examined at various stages of disease progression and compared to age-matched wild-type controls. Akt and phospho-Akt increased significantly with disease progression but these elevations were not accompanied by alterations in downstream proteins such as p70s6K or BAD. These findings suggest a potential role of Akt in muscle undergoing progressive denervation. I further determined whether the increase in Akt was localized to innervated or denervated muscle cells. Akt-irnmunofluorescence was localized primarily to cells staining positive for neural cell adhesion molecule (NCAM), a marker of skeletal muscle denervation. These localized elevations in Akt may reflect compensatory changes occurring in muscle in response to denervation, potentially in an attempt to maintain muscle mass or alternately, to promote cell survival.