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

Abstract

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.