Selective enhancement of tubulin gene expression and increase in oligo(dT)-bound RNA in the rat brain after nigrostriatal pathway unilateral lesion and treatment with ganglioside.

Partial hemitransection of the rat nigrostriatal pathway has been applied to study changes in the expression of tubulin and actin cytoskeletal genes. RNA was isolated from ipsilateral and contralateral structures of substantia nigra and striatum tissues of lesioned or sham-operated animals by a combined proteinase K and oligo(dT)-cellulose affinity purification procedure. A significant increase in the oligo(dT)-cellulose-eluted RNA was observed in the lesioned substantia nigra and striatal tissues compared to naive controls. By 5 days, the RNA content of the lesioned nigra reached a value of 96-114.5 micrograms/mg DNA compared to 45.7-52.9 micrograms/mg DNA. Administration of GM1 gangliosides at daily intervals resulted by day 5 in a further increase (131.8-141.5 micrograms/mg DNA) in the RNA content of the lesioned but also of the sham-operated (81.9-97.8 micrograms/mg DNA) animals. By 18 hr, the lesioned nigra exhibited a four-fold increase in tubulin messenger RNA (mRNAtub) gene expression in comparison to the sham-operated animals. The substantia nigra tissue of GM1-treated animals exhibited a hybridization value for mRNAtub twice as high compared to GM1-untreated, lesioned animals. The effect of GM1 appeared selective for alpha-tubulin and beta-tubulin compared to actin transcript. The latter was also elevated in the lesioned nigra tissue above the naive or sham-operated animals. The data suggest that, after injury, cytoskeletal RNA transcripts are elevated and that GM1 may play a role in the regulation of their steady-state levels.