Sodium valproate increases the brain isoform of glycogen phosphorylase: looking for a compensation mechanism in @entity9847 using a XXXX primary skeletal-muscle culture in vitro.

@entity1 @entity71660 @entity4431 @entity19 @entity1295 @entity9958 @entity36191 @entity196 @entity5925 @entity74 @entity9847 @entity35 @entity121 @entity27038
@entity9847 , also termed 'glycogen storage disease @entity196 ', is a @entity121 carbohydrate metabolism caused by @entity74 of the muscle-specific isoform of glycogen phosphorylase (GP-MM). It is an @entity74 that is caused by mutations in the @entity71660 gene and typically presents with exercise intolerance, i.e. episodes of early exertional @entity1295 frequently accompanied by @entity5925 and @entity9958 . Muscle biopsies from affected individuals contain subsarcolemmal deposits of glycogen. Besides GP-MM, two other GP isoforms have been described: the liver (GP-LL) and brain ( @entity27038 ) isoforms, which are encoded by the @entity36191 and @entity27038 genes, respectively; @entity27038 is the main GP isoform found in @entity1 and @entity35 foetal tissues, including the muscle, although its postnatal expression is dramatically reduced in the vast majority of differentiated tissues with the exception of brain and heart, where it remains as the major isoform. We developed a cell culture model from knock-in @entity9847 @entity19 that mimics the glycogen accumulation and @entity4431 observed in skeletal muscle from individuals with @entity9847 . We treated @entity19 primary skeletal muscle cultures in vitro with sodium valproate (VPA), a histone deacetylase inhibitor. After VPA treatment, myotubes expressed @entity27038 and a dose-dependent decrease in glycogen accumulation was also observed. Thus, this in vitro model could be useful for high-throughput screening of new drugs to treat this disease. The immortalization of these primary skeletal muscle cultures could provide a never-ending source of cells for this experimental model. Furthermore, VPA could be considered as a gene-expression modulator, allowing compensatory expression of @entity27038 and decreased glycogen accumulation in skeletal muscle of individuals with @entity9847 .
