Insulin-like growth factor-I as a promoting factor for cerebellar Purkinje cell development.

Abstract

In the mammalian CNS, the peptide hormone insulin-like growth factor-I (IGF-I) is synthesized in a certain subset of neurons and, it has been suggested, serves as a local neurotrophic factor. A postnatal increase in the expression of IGF-I and the type-1 IGF receptors (IGFR1) in the cerebellar cortex and its related brain regions indicates that developing cerebellar Purkinje cells (PC) may be an important target of IGF-I. However, little is known about how IGF-I influences PC development. Here we addressed this question, using a reduced environment of cerebellar neuron culture derived from perinatal mice. IGF-I exogenously applied at a physiological concentration (10 nm) greatly promoted the dendritic growth and survival of the PCs. By contrast, IGF-I only slightly promoted the somatic growth and little affected the maturation of the electrophysiological excitability of the PCs. The closely related hormone insulin had weaker promoting effects than did IGF-I. IGF-I appeared to at least bind to IGFR1 and to up-regulate the signalling pathways involving the phosphoinositide 3-kinase (PI3-K), mitogen-activated protein kinase (MAPK), p38 kinase (p38K), and an unknown signalling molecule(s). These signalling pathways may be coupled to the individual aspects of PC development in different manners and this may explain the difference in effects of IGF-I among these aspects. These findings suggest that IGF-I serves as a promoting factor for PC development, particularly postnatal survival and dendritic growth.