TRANSCRIPTION OF THE HUNTINGTON-DISEASE GENE DURING THE QUINOLINIC ACID EXCITOTOXIC CASCADE

ALTHOUGH Huntington disease (HD) is characterized by the selective neu rodegeneration of the basal ganglia and cerebral cortex, efforts to de fine the disease pathology have been complicated by the widespread exp ression of the disease gene (IT15) throughout the body. In this study, we examined IT15 mRNA levels during the quinolinic acid (QA) excitoto xic cascade to determine whether neuronal and/or glial expression is r egulated by neurodegeneration. Following an initial increase between 1 h and 6 h, IT15 mRNA levels declined in a pattern homologous to a gro up of neuron-specific genes. Decreased mRNA levels after 24 h demonstr ated that glial transcription is not activated by neurodegeneration or gliosis. The 1 h and 24 h mRNA levels strongly suggest that IT15 tran scription preferentially localizes to degenerating neurons.