Dietary NaCl supplementation prevents muscle necrosis in a mouse model of Duchenne muscular dystrophy

1 Department of Degenerative Neurological Disease, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; 2 Hitachi High Technologies, Ibaraki, Japan Submitted 5 October 2004 ; accepted in final form 13 September 2005 The mdx mouse is an animal model for Duchenne muscular dystrophy. Mdx mice fed a 12% NaCl diet from birth up to 20 days of age (mdx-Na mice) had an 50% reduction in serum creatine kinase (CK) activity compared with mdx mice fed a standard diet. Most notably, necrotic fibers in tibialis anterior (TA) muscle of mdx-Na mice were reduced by 99% and were similar in control mice. These mdx mice displayed significantly elevated blood Ca 2+ and Na + levels, while the total calcium content of their TA muscle was reduced to the level of control mice. In addition, mdx-Na mice had elevated zinc and magnesium contents in their TA muscle. These results suggest that elevated serum Na + leads to Ca 2+ extrusion from muscle via the Na + /Ca 2+ exchanger causing a decrease in intracellular Ca 2+ levels and an increase in blood Ca 2+ levels. Extracellular Ca 2+ and, in addition, Zn 2+ and Mg 2+ might also contribute to the stabilization of the cell membrane. Other possibilities explaining the surprisingly efficacious beneficial effect of dietary sodium exist and are discussed. therapy; calcium and zinc; potassium; blood; serum creatine kinase activity Address for reprint requests and other correspondence: Mizuko Yoshida, Department of Degenerative Neurological Disease, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187–8052, Japan (e-mail: yoshidam{at}ncnp.go.jp )