Treatment with inhibitors of the NF-κB pathway improves whole body tension development in the mdx mouse

• Published in: Neuromuscular disorders : NMD Vol. 19; no. 2; pp. 131 - 139
• Main Authors: Siegel, Ashley L, Bledsoe, Cathy, Lavin, Jesse, Gatti, Francesca, Berge, Jonas, Millman, Gregory, Turin, Eric, Winders, W. Tyler, Rutter, John, Palmeiri, Beniamino, Carlson, C. George
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-02-2009
• Subjects: Mdx mouse; Muscle function; Muscular dystrophy; Neurology; NF-κB; Pyrollidine dithiocarbamate; Ursodeoxycholic acid; Whole body tension; Mdx mouse; NF-κB; Pyrollidine dithiocarbamate; Muscle function; Whole body tension; Muscular dystrophy; Ursodeoxycholic acid
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2008.10.006

Abstract The whole body tension (WBT) method was used to evaluate the hypothesis that long term treatment with NF-κB inhibitors improves the total forward pulling tension exerted by the limb musculature of the mdx mouse. Mdx mice exhibited significantly reduced WBT values and more profound weakening during the course of generating multiple forward pulling movements than age-matched nondystrophic mice. Long term treatment with the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) did not significantly reduce nuclear p65 activation in the costal diaphragm, but increased WBT by 12% in mature (12 month) mice. Daily treatment (30 days) of 1 month old mdx mice with the inhibitor ursodeoxycholic acid (UDCA) reduced costal diaphragm nuclear p65 activation by 40% and increased WBT by 21%. These results indicate that treatment with NF-κB inhibitors improves WBT in the mdx mouse and further establishes the utility of the WBT procedure in assessing therapeutic efficacy.