Rapid upregulation of the Pi isoform of glutathione-S-transferase in mouse brains after withdrawal of the neurotoxicant, cuprizone

Cuprizone intoxication has been used as a model for reversible demyelination in the CNS. During the course of cuprizone intoxication, the glutathione-S-transferase isoform, Pi, normally an oligodendrocytic marker, appears in reactive astrocytes (Cammer and Zhang, 1993). The present experiments address the changes in expression of Pi after removal of cuprizone from the diet of the affected mice. In order to localize Pi message, a riboprobe was prepared and in situ hybridization (ISH) performed. Western blots and immunocytochemistry were used to examine Pi protein and other glial cell markers. The data indicated that Pi protein increased during the first 2 d after withdrawal of the toxicant, when the level of the myelin marker, 2', 3'-cyclic nucleotide-3'-phosphohydrolase, remained minimal. Results of ISH suggested that levels of Pi message in the corpus striatum decreased during cuprizone feeding and began to recover within 2 d after withdrawal of the toxicant. Both microglia and astrocytes appeared during the first week of cuprizone administration and persisted during two to three additional weeks on cuprizone. Reactive astrocytes remained in the tissue for at least 6 wk after cuprizone was withdrawn, while microglia receded within days. The findings suggest that astrocytes continue to express Pi after withdrawal of cuprizone.