The Effects of Endurance Exercise on Lactatedehydrogenase-A and Lactatedehydrogenase-B Gene Expression in Skeletal Muscle of Asymptomatic and Symptomatic Huntington's Disease Mutation Carriers

Abstract

Huntington's Disease (HD) is an incurable autosomal dominant hereditary disease. Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is a master regulator of mitochondrial function and lactate metabolism through gene expression of Lactatedehydrogenase (LDH) A and B. PGC-1alpha function is altered in HD, however its role is not yet fully understood. To further investigate the metabolic changes in HD I compared the response of whole body lactate, as well as skeletal muscle gene expression of LDH A and LDH B to endurance exercise in presymptomatic and symptomatic HD mutation carriers to a group of healthy controls. Lactate response was altered in symptomatic gene carriers and LDH A response was impaired in both presymptomatic and symptomatic gene carriers. LDH B gene expression wasn't influenced, raising the question whether and when LDH A and LDH B response and therefore PGC-1alpha function are altered in HD. This calls for further investigation of Lactate and LDH A and B response to exercise in Huntington's Diseases, as well as PGC-1alpha function and may lead to a better understanding of the disease's underlying pathomechanisms.