Insulin-like growth factor I restores motor coordination in a rat model of cerebellar ataxia

Insulin-like growth factor I restores motor coordination in a rat model of cerebellar ataxia

Laboratory of Cellular and Molecular Neuroendocrinology, Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid 28002, Spain

Edited by Dale Purves, Duke University Medical Center, Durham, NC, and approved November 26, 1997 (received for review June 12, 1997)

Abstract

We tested the potential of insulin-like growth factor I (IGF-I) to induce functional recovery in an animal model of cerebellar ataxia because this motor impairment is accompanied in humans and rodents by distinct changes in several components of the IGF-I trophic system. Rats rendered ataxic by deafferentation of the cerebellar cortex with 3-acetylpyridine recovered motor function after IGF-I was administered, as determined by behavioral and electrophysiological tests. When treated with IGF-I, inferior olive neurons, the targets of the neurotoxin, were rescued to various degrees (from 92 to 27% of surviving neurons), depending on the time that treatment with IGF-I was initiated. Furthermore, full recovery was obtained regardless of the route by which the trophic factor was administered (intraventricular or subcutaneous) even in rats with severe neuronal loss. These results suggest that human ataxia could be treated with IGF-I by a simple procedure.

Footnotes

↵ * To whom reprint requests should be addressed at: Laboratory of Cellular and Molecular Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientificas, Avenida Doctor Arce 37, 28002 Madrid, Spain. e-mail: torres{at}cajal.csic.es.
This paper was submitted directly (Track II) to the Proceedings Office.
Abbreviations: IGF-I, insulin-like growth factor I; 3AP, 3-acetylpyridine; i.c.v., intracerebroventricular; GABA, γ-aminobutyric acid.