Eur J Anat, 2 (3): 147-158 (1998)

Receptor-mediated internalization of insulin-like growth factor-l in neurons and glia of the central nervous system of the adult rat

M.C. Fernández-Galaz, I. Torres-Alemán and L.M. García-Segura

Laboratory of Cellular and Molecular Neuroendocrinology, Instituto Cajal, C.S.I.C., Avenida Dr. Arce 37, E-28002 Madrid, Spain

ABSTRACT Insulin-like growth factor-I is produced in the developing brain where it acts as a trophic sig­ nal for different neuronal and glial populations. While its synthesis declines in most brain areas with adulthood, expression of its receptor per­ sists, together with a broad distribution of cells imrnunoreactive for the peptide. In the adult brain, insulin-like growth factor-I acts as a neu­ rornodulator and a neuroendocrine messenger and is also involved in neurodegenerative pro­ cesses, reducing neuronal loss after brain injury, To determine whether adult brain cells are able to uptake insulin-like growth factor-I from the cerebrospinal fluid, the peptide was labeled with digoxigenin and injected into the lateral cerebral ventricle. A large population of ependymal cells, glial cells and neurons located throughout the entire central nervous system accumulated labeled peptide. Their distribution,- corresponded to that of cells expressing insulin­like growth factor-I receptors and also to the distribution of cells immunoreactive for the pep­ tide in the adult rat brain. Accumulation of the growth factor was receptor-media red, since it was blocked by simultaneous intracerebroven­ tricular injection of unlabeled peptide and by JBl, a specific antagonist of insulin-like growth factor-I receptors. Insulin, at a concentration known to interact with insulin-like growth fac­ tor-I receptors also blocked accumulation of the growth factor. These results indicate that insulin­ like growth factor-I is internalized by its target cells in the adult central nervous system and that intracerebroventricular injections are a useful mean to dispense the growth factor to its target cells.

Keywords: Insulin-like growth factor I - Insulin - Growth factors - Cerebrospinal fluid.