Survival of Purkinje Cells in Cerebellar Cultures is Increased by Insulin-like Growth Factor I.

Insulin-like growth factor I (IGF-I) is a trophic factor for both neurons and glia. Its presence in the developing and adult cerebellum suggests a role for this growth factor in this area of the brain. Recently, we have described the existence of an IGF-I-containing pathway in afferents of Purkinje neurons arising from the inferior olive. In addition, IGF-I receptors are present in the molecular layer of the cerebellar cortex. These observations prompted us to investigate whether the Purkinje cell is a target for IGF-I. Addition of IGF-I to rat cerebellar cultures produced a 7-fold increase in the number of Purkinje cells (calbindin-positive) together with an increase in the calbindin content of the cultures. IGF-I also doubled the number of surviving neurons and produced a moderate, non-significant increase in [3H]thymidine incorporation by the cultures. On the other hand, basic fibroblast growth factor (bFGF), which is also present in the cerebellum, produced a dramatic increase in both the proportion of astrocytes and in the mitotic activity of the cultures, without affecting neuron survival. We conclude that IGF-I is a specific promoter of Purkinje cell survival and that its effects differ from those produced by bFGF in fetal cerebellar cultures. These findings reinforce our hypothesis that the Purkinje cell is a target neuron for IGF-I action in the developing cerebellum.