Developmental patterns in the rat cerebellum after cis-dichlorodiammineplatinum treatment

A cytochemical study was made of some metabolic enzymes in the cerebellar neurons during postnatal ontogenesis after injection of cis-dichlorodiammineplatinum into 10-day-old rats. The profiles during development of neuron-specific enolase immunoreactivity (involved in the glycolytic pathway), dihydrofolate reductase activity (involved in the metabolism of nucleic acids and folate) and dipeptidylaminopeptidase II activity were determined in lobules V-VII of cerebellar vermis. At different developmental stages, treated rats had folia in which the morphology and cytochemical responses of Purkinje neurons were greatly affected. On postinjection day 1 (PD 11), only neuron-specific enolase immunoreactivity was changed, reactions being more intense at the basal pole, which was abnormally enlarged in several neurons. Seven days after treatment (PD 17), the dihydrofolate reductase reaction showed weakly positive cells with small grains of formazan in the perinuclear regions and dipeptidylaminopeptidase II activity, which had appeared at this time in some cells of the controls, was not observed. On PD 25 and PD 35, Purkinje cells, probably undergoing clear degeneration, were negative or very weakly positive in all the reactions. Some tracts of folia had no Purkinje cells. These results suggest that cis-dichlorodiammineplatinum affects the differentiation of Purkinje neurons and interferes first with the glycolytic enzyme and then with some enzymes of the synthetic and catabolic machinery, leading to cellular dysfunction and degeneration.