BACKGROUND: Loss of dystrophin profoundly affects muscle function and cognition. Changes in the dystrophin-glycoprotein complex (DGC) including disruption of nitric oxide synthase (NOS-1) may result from loss of dystrophin or secondarily after muscle damage. Disruptions in NOS-1 and beta-dystroglycan (bDG) were examined in developing diaphragm, quadriceps, and two brain regions between control and mdx mice at embryonic day E18 and postnatal days P1, P10, and P28. Age-dependent differential muscle loading allowed us to test the hypothesis that DGC changes are dependent on muscle use. RESULTS: Muscle development, including loss of central nucleation and the localization of NOS-1 and bDG, was earlier in diaphragm than quadriceps; these features were differentially disrupted in dystrophic muscles. The NOS-1/bDG ratio, an index of DGC stability, was higher in dystrophic diaphragm (P10-P28) and quadriceps (P28) than controls. There were also distinct regional differences in NOS-1 and bDG in brain tissues with age and strain. NOS-1 increased with age in control forebrain and cerebellum, and in mdx cerebellum; NOS-1 and bDG were higher in control than mdx mouse forebrain. CONCLUSIONS: Important developmental changes in structure and muscle DGC preceded the hallmarks of dystrophy, and are consistent with the impact of muscle-specific differential loading during maturation.
BACKGROUND: Loss of dystrophin profoundly affects muscle function and cognition. Changes in the dystrophin-glycoprotein complex (DGC) including disruption of nitric oxide synthase (NOS-1) may result from loss of dystrophin or secondarily after muscle damage. Disruptions in NOS-1 and beta-dystroglycan (bDG) were examined in developing diaphragm, quadriceps, and two brain regions between control and mdx mice at embryonic day E18 and postnatal days P1, P10, and P28. Age-dependent differential muscle loading allowed us to test the hypothesis that DGC changes are dependent on muscle use. RESULTS: Muscle development, including loss of central nucleation and the localization of NOS-1 and bDG, was earlier in diaphragm than quadriceps; these features were differentially disrupted in dystrophic muscles. The NOS-1/bDG ratio, an index of DGC stability, was higher in dystrophic diaphragm (P10-P28) and quadriceps (P28) than controls. There were also distinct regional differences in NOS-1 and bDG in brain tissues with age and strain. NOS-1 increased with age in control forebrain and cerebellum, and in mdx cerebellum; NOS-1 and bDG were higher in control than mdx mouse forebrain. CONCLUSIONS: Important developmental changes in structure and muscle DGC preceded the hallmarks of dystrophy, and are consistent with the impact of muscle-specific differential loading during maturation.
Authors: Erik P Rader; Rolf Turk; Tobias Willer; Daniel Beltrán; Kei-Ichiro Inamori; Taylor A Peterson; Jeffrey Engle; Sally Prouty; Kiichiro Matsumura; Fumiaki Saito; Mary E Anderson; Kevin P Campbell Journal: Proc Natl Acad Sci U S A Date: 2016-09-13 Impact factor: 11.205
Authors: Paz García-Campos; Ximena Báez-Matus; Carlos Jara-Gutiérrez; Marilyn Paz-Araos; César Astorga; Luis A Cea; Viviana Rodríguez; Jorge A Bevilacqua; Pablo Caviedes; Ana M Cárdenas Journal: Int J Mol Sci Date: 2020-06-16 Impact factor: 5.923