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Current Research:
A loss of muscle mass is frequently associated with disease, with the removal of weight bearing such as occurs in the microgravity environment of space, and with aging. The cellular and molecular mechanisms underlying the loss of muscle are studied in dystrophic mice, aging rodents and in rodent models of simulated microgravity. In addition to the loss of mass, under many circumstances, unexplained muscle weakness remains when force is normalized by muscle cross-sectional area. The weakness appears to be due in large part to changes that occur with within single muscle fibers. Consequently, we are probing the effects of injury, dystrophic disease, unloading, and aging on the underlying contractile apparatus, including the coupling between muscle fiber excitation and the release of activating Ca2+ into the myoplasm. The latter experiments involve monitoring intracellular [Ca2+] and measuring mechanics simultaneously.
Exercise-induced skeletal muscle injury is initiated by the mechanical disruption of the muscle fiber ultrastructure. The initial mechanical damage initiates a cascade of events including an inflammatory response and degeneration of the damaged fibers. Recovery occurs through a process of regeneration that in many ways recapitulates events of myogenesis. In young control animals, muscles are relatively resistant to damage and recover completely within days to weeks. The frequency and magnitude of injury are increased by aging and disease and decreased through exercise training. The mechanisms underlying differences in susceptibility to injury are investigated using a combination of in vivo and in vitro experiments. Understanding the tissue, cellular, and molecular adaptations responsible for the protection from contraction-induced injury provided by exercise training is of particular interest.
A great deal of latitude is typically given to students and postdoctoral fellows for new and creative experiments, at the organism, tissue, cellular or molecular levels, designed to address questions of the basic properties of aging, unloaded, or dystrophic muscle.
Representative
Publications:
Pizza F.X., Koh T.J., McGregor S.J., and Brooks S.V. Muscle inflammation following passive stretches, isometric contractions, and lengthening contractions. J Appl Physiol 92:1873-1878, 2002.
DelloRusso C., Scott J., Hartigan-O'Connor D., Salvatori G., Barjot C., Robinson A.S., Crawford R.C., Brooks S.V., and Chamberlain J.S. Functional correction of adult mdx mouse muscle using gutted adenoviral vectors expressing full-length dystrophin. Proc Natl Acad Sci 99:12979–12984, 2002.
Koh T.J., Peterson J.M., Pizza F.X., and Brooks S.V. Passive stretches protect skeletal muscles of adult and old mice from lengthening contraction-induced injury. J Gerontol 58A:B592-B597, 2003.
Consolino, C.M. and Brooks S.V. Susceptibility to injury induced by single stretches of maximally activated muscles of mdx mice. J Appl Physiol 96:633-638, 2004.
Consolino C.M., Duclos F., Lee J., Williamson R., Campbell K.P., and Brooks S.V. Limb muscles of mice deficient in α-sarcoglycan maintain large muscle masses and near control levels for force throughout the life span. Physiological Genomics, 22:244-256, 2005.
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