IGF-1 influences olfactory bulb maturation. Evidence from anti-IGF-1 antibody treatment of developing grafts in oculo.
Recent studies have indicated that both insulin-like growth factor-1 (IGF-1) and IGF-1 receptor mRNA are abundant in developing and adult olfactory bulbs, and that IGF-1 receptor mRNA is abundant in the prenatal cerebral cortex. To examine the potential role of IGF-1 in development of a central nervous system region rich in IGF-1 and its receptor (the olfactory bulb), as compared to one in which IGF-1 is less abundant (the cerebral cortex), tissue pieces of these two central nervous system areas from E15-E17 rat fetuses were transplanted into the anterior chamber of the eye of adult host rats. The transplants were treated with either a total of 300 ng truncated IGF-1, two different IGF-1 polyclonal antisera, two different non-immune sera, a total of 15 micrograms IGF binding protein-1, or vehicle alone. Treatments were administered by preincubation just prior to grafting and by 5 microliters injections into the anterior chamber on days 5, 10 and 15 postgrafting. Olfactory bulb grafts treated with either of the two IGF-1 antisera grew significantly larger than grafts receiving any other treatment. No enhancement of graft size was seen in E16-E17 parietal cortex grafts after IGF-1 antibody treatment. Immunohistochemical studies revealed no difference between the treatments with regard to glial fibrillary acidic protein-, tyrosine hydroxylase- or neurofilament-immunoreactivity within the olfactory bulb grafts. Since, in the olfactory bulb the presumed reduction of endogenous IGF-1 achieved by antibody treatment caused enhanced growth, we suggest that the presence of appropriate endogenous levels of IGF-1 in this area induces maturation. This mechanism is not operative in all brain areas since it was not seen in cortex cerebri grafts. Thus, endogenous IGF-1 appears to influence brain development in a regionally specific manner.
Giacobini
M M
MM
Department of Neuroscience/Histology, Karolinska Institute, Stockholm, Sweden.
Zetterström
R H
RH
Young
D
D
Hoffer
B
B
Sara
V
V
Olson
L
L
D000818:Animals; D000906:Antibodies; D016380:Brain Tissue Transplantation; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008297:Male; D009799:Ocular Physiological Phenomena; D009830:Olfactory Bulb / Q000502:physiology*; D010296:Parietal Lobe / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D007334:Insulin-Like Growth Factor I