Insulin-like growth factor I modulates c-Fos induction and astrocytosis in response to neurotoxic insult.
Insulin-like growth factor I participates in the cellular response to brain insult by increasing its messenger RNA expression and/or protein levels in the affected area. Although it has been suggested that insulin-like growth factor I is involved in a variety of cellular responses leading to homeostasis, mechanisms involved in its possible trophic effects are largely unknown. Since activation of c-Fos in postmitotic neurons takes place both in response to insulin-like growth factor I and after brain injury, we have investigated whether this early response gene may be involved in the actions of insulin-like growth factor I after brain insult. Partial deafferentation of the cerebellar cortex by 3-acetylpyridine injection elicited c-Fos protein expression on both Purkinje and granule cells of the cerebellar cortex. This neurotoxic insult also triggered gliosis, as determined by an increased number of glial fibrillary acidic protein-positive cells (reactive astrocytes) in the cerebellar cortex. When 3-acetylpyridine-injected animals received a continuous intracerebellar infusion of either a peptidic insulin-like growth factor I receptor antagonist or an insulin-like growth factor I antisense oligonucleotide for two weeks through an osmotic minipump, c-Fos expression was obliterated while reactive gliosis was greatly increased. On the contrary, continuous infusion of insulin-like growth factor I significantly decreased reactive gliosis without affecting the increase in c-Fos expression. These results indicate that insulin-like growth factor I is involved in both the neuronal (c-Fos) and the astrocytic (glial fibrillary acidic protein) activation in response to injury.
Fernandez
A M
AM
Laboratory of Cellular and Molecular Neuroendocrinology, Cajal Institute, CSIC, Madrid, Spain.
Garcia-Estrada
J
J
Garcia-Segura
L M
LM
Torres-Aleman
I
I
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D005911:Gliosis / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D011994:Recombinant Proteins; C010835:3-acetylpyridine; D007334:Insulin-Like Growth Factor I