Insulin-like growth factor-I (IGF-I) ameliorates and IGF binding protein-1(IGFBP-1) exacerbates the effects of undernutrition on brain growth duringearly postnatal life: Studies in IGF-I and IGFBP-1 transgenic mice

Insulin-like,growth factor-I (IGF-I) plays an important role in the stimula tion of postnatal brain growth. In transgenic (Tg) mice, IGF-I overexpressi on stimulates postnatal brain growth, whereas decreased IGF-I availability caused by ectopic brain expression of IGF binding protein-1 [(IGFBP-1), an inhibitor of IGF-I action] retards postnatal brain growth. Because undernut rition during early postnatal development profoundly retards growth and mat uration of the brain in rodents, we sought to determine the influence of IG F-I on undernutrition-induced brain growth retardation. Caloric restriction was imposed on IGF-I Tg mice, IGFBP-1 Tg mice, and their non-Tg littermate s by separating half of each litter from their dams during the suckling per iod, postnatal d 1 to 21. Undernutrition reduced the brain growth of each g roup of mice, but the growth of undernourished IGF-I Tg mice was comparable to that of well-fed control mice (increased 4.13- and 4.22-fold, respectiv ely) and greater than that of undernourished control mice (increased 3.45-f old), whereas undernourished IGFBP-1 Tg mice exhibited less growth (increas ed 3.15-foId) than undernourished control mice. When the effects of undernu trition were examined in specific brain regions of each group, the same pat tern was observed, and IGF-I was found to be more effective in preserving t he growth of the regions with the highest transgene expression (cerebral co rtex, hippocampus, and diencephalon). Despite undernutrition, IGF-I transge ne expression stimulated overgrowth of these regions as well as that of the posterior medial barrel subfield, a somatosensory area of the cerebral cor tex in which IGF-I may be especially important in development. These data i ndicate that IGF-I can ameliorate the brain growth retardation caused by un dernutrition imposed during development, although it is unclear whether IGF -I directly opposes the impact of undernutrition or acts independently of n utritional status. Nonetheless, these findings raise the possibility that t he relatively high IGF-I expression during early postnatal Life may be resp onsible for sparing the brain from the full impact of undernutrition during this time in development.