Transcription of the Huntington disease gene during the quinolinic acid excitotoxic cascade.
Although Huntington disease (HD) is characterized by the selective neurodegeneration of the basal ganglia and cerebral cortex, efforts to define the disease pathology have been complicated by the widespread expression of the disease gene (IT15) throughout the body. In this study, we examined IT15 mRNA levels during the quinolinic acid (QA) excitotoxic cascade to determine whether neuronal and/or glial expression is regulated by neurodegeneration. Following an initial increase between 1 h and 6 h, IT15 mRNA levels declined in a pattern homologous to a group of neuron-specific genes. Decreased mRNA levels after 24 h demonstrated that glial transcription is not activated by neurodegeneration or gliosis. The 1 h and 24 h mRNA levels strongly suggest that IT15 transcription preferentially localizes to degenerating neurons.
Carlock
L
L
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Walker
P D
PD
Shan
Y
Y
Gutridge
K
K
D000818:Animals; D015152:Blotting, Northern; D015870:Gene Expression; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D009410:Nerve Degeneration; D017378:Quinolinic Acid / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics*
D012333:RNA, Messenger; D017378:Quinolinic Acid