The dystroglycan protein complex provides a link between the cytoskeleton and the extracellular matrix (ECM). Defective O-glycosylation of a-dystroglycan (a-DG) severs this link leading to muscular dystrophies named dystroglycanopathies. These are characterized not only by muscle degeneration, but also by brain and ocular defects. In brain and retina, a-DG and ECM molecules are enriched around blood vessels where they may be involved in localizing the inwardly rectifying potassium channel, Kir4.1, and aquaporin channel, AQP4, to astrocytic endfeet. To investigate in vivo the role of ECM ligand-binding to glycosylated sites on a-DG in the polarized distribution of these channels, we used the Large myd mouse, an animal model for dystroglycanopathies. We found that Kir4.1 and AQP4 are lost from astrocytic endfeet in brain whereas significant labeling for these channels is detected at similar cell domains in retina. Furthermore, while both a-and b1-syntrophins are lost from perivascular astrocytes in brain, labeling for b1-syntrophin is found in retina of the Large myd mouse. These findings show that while ligand-binding to the highly glycosylated isoform of a-DG in concert with a-and b1-syntrophins is crucial for the polarized distribution of Kir4.1 and AQP4 to functional domains in brain, distinct mechanisms may contribute to their localization in retina.

To describe how inflammation affects muscle adaptation and performance in people with chronic obstructive pulmonary disease. In chronic obstructive pulmonary disease, an increasingly sedentary lifestyle is a primary contributor to muscle dysfunction that results in a loss of mobility and independence and, ultimately, mortality. Given the systemic chronic inflammation and profound limb muscle atrophy in chronic obstructive pulmonary disease, it is tempting to speculate that the inflammatory process is deleterious to skeletal muscle. In healthy people, however, the inflammatory process initially is dominated by a destructive phase that is tightly regulated and modulates a reparative, regenerative phase. Although the inflammatory process and associated oxidative stress is more closely connected to muscle wasting in animal models of chronic obstructive pulmonary disease, the causative role of inflammation toward muscle atrophy and weakness in people with chronic obstructive pulmonary disease has not been definitively shown. Anti-inflammatory interventions aimed toward tempering muscle wasting and weakness in chronic obstructive pulmonary disease may not prove to be beneficial because of longer-term disruption of the regeneration of muscle tissue. Temporally and spatially targeted interventions aimed toward ameliorating oxidative stress, such as antioxidants, nutritional supplements, and chronic exercise training, may optimize outcomes toward maintaining muscle mass and performance.