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.
Nieto-Bona
M P
MP
Laboratory of Cellular and Molecular Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Busiguina
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S
Torres-Aleman
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D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D064026:Calbindins; D003720:Densitometry; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000502:physiology*; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009847:Olivary Nucleus / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D064026:Calbindins; D016376:Oligonucleotides, Antisense; D064030:S100 Calcium Binding Protein G; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007334:Insulin-Like Growth Factor I