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 ^[1] ; I. Torres-Alemán ^[1] ; L.M. García-Segura ^[1]
  1. [1] Laboratory of Cellular and Molecular Neuroendocrinology, Instituto Cajal, C.S.I.C.
• Localización: European Journal of anatomy, ISSN-e 1136-4890, Vol. 2, Nº. 3, 1998, págs. 147-158
• Idioma: inglés
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• Resumen

  • 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.