IGF-1 influences olfactory bulb maturation. Evidence from anti-IGF-1 antibody treatment of developing grafts in oculo

Abstract

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 μg IGF binding protein-1, or vehicle alone. Treatments were administered by preincubation just prior to grafting and by 5 μl 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.