Insulin-like growth factor I is an afferent trophic signal that modulates calbindin-28kD in adult Purkinje cells

Recent evidence suggests that Purkinje cells are specific targets of insulin‐like growth factor I (IGF‐I) through their entire life span. During development, Purkinje cell numbers and their calbindin‐28kD content increase after IGF‐I treatment in culture. In the adult, part of the IGF‐I present in the cerebellum is transported from the inferior olive, and modulates Purkinje cell function. We investigated whether IGF‐I produced by inferior olive neurons and transported to the contralateral cerebellum through climbing fibers may modulate the levels of calbindin‐28kD in the cerebellum of adult animals. Twenty‐four hr after injection of an antisense oligonucleotide of IGF‐I into the inferior olive, both IGF‐I and calbindin‐28kD levels in the contralateral cerebellar lobe were significantly reduced, while the number of calbindin‐positive Purkinje cells was unchanged. The effect of the antisense on IGF‐I levels was fully reversed 3 days after its injection into the inferior olive, with a postinhibitory rebound observed at this time, while calbindin‐28kD levels slowly returned to control values. A control oligonucleotide did not produce any change in either IGF‐I or calbindin‐28kD content in the cerebellum. These results indicate that normal levels of IGF‐I in the inferior olive are necessary to maintain appropriate levels of IGF‐I in the cerebellum and of calbindin‐28kD in the Purkinje cell. These results also extend our previous findings on the existence of an olivo‐cerebellar IGF‐I‐containing pathway with trophic influence on the adult Purkinje cell. © 1995 Wiley‐Liss, Inc.