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 i nsulin-like growth factor I (IGF-I) through their entire life span, Du ring development, Purkinje cell numbers and their calbindin-28kD conte nt increase after IGP-I treatment in culture, In the adult, part of th e IGF-I present in the cerebellum is transported from the inferior oli ve, and modulates Purkinje cell function, We investigated whether IGP- I produced by inferior olive neurons and transported to the contralate ral cerebellum through climbing fibers may modulate the levels of calb indin-28kD in the cerebellum of adult animals, Twenty-four hr after in jection of an antisense oligonucleotide of IGF-I into the inferior oli ve, both IGF-I and calbindin-28kD levels in the contralateral cerebell ar lobe were significantly reduced, while the number of calbindin-posi tive Purkinje cells was unchanged, The effect of the antisense on IGF- I levels was fully reversed 3 days after its injection into the inferi or olive, with a postinhibitory rebound observed at this time, while c albindin-28kD levels slowly returned to control values, A control olig onucleotide did not produce any change in either IGF-I or calbindin-28 kD content in the cerebellum, These results indicate that normal level s 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 Purkin je cell, These results also extend our previous findings on the existe nce of an olive-cerebellar IGF-I-containing pathway with trophic influ ence on the adult Purkinje cell. (C) 1995 Wiley-Liss, Inc.