BRAIN METABOLISM IS ABNORMAL IN THE MDX MODEL OF DUCHENNE MUSCULAR-DYSTROPHY

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder prim arily affecting young boys, often causing mental retardation in additi on to the well-known progressive muscular weakness. Normal dystrophin expression is lacking in skeletal muscle and the CNS of both DMD child ren and the mdx mouse model. To date, P-31-magnetic resonance spectros copy (MRS) has shown in vivo several abnormalities within skeletal mus cle of mdx mice and DMD boys. In this study, we determined whether sim ilar abnormalities occur in mdx brain in vivo by using P-31-MRS in add ition to metabolite and enzyme analysis to study cerebral metabolism A n increased inorganic phosphate (P-i)/phosphocreatine (PCr) and pH was found in vivo for mdx brain compared with controls, and biochemical a nalysis showed a reduction in total creatine, an increased extracellul ar and decreased intracellular volume in mdx brain. No differences wer e found in any glycolytic or mitochondrial maximal enzyme activities. These changes are discussed with respect to the biochemical changes fo und in muscle from DMD patients and mdx mice. It is proposed that thes e biochemical changes may be a factor in the reduced cognitive capacit y of mdx mice and some DMD children.