Insulin-like growth factor-I (
IGF-I) plays an important role in the stimulation of postnatal brain growth. In transgenic (Tg) mice,
IGF-I overexpression 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
undernutrition during early postnatal development profoundly retards growth and maturation of the brain in rodents, we sought to determine the influence of
IGF-I on
undernutrition-induced brain growth retardation.
Caloric restriction was imposed on
IGF-I Tg mice,
IGFBP-1 Tg mice, and their non-Tg littermates by separating half of each litter from their dams during the suckling period, postnatal d 1 to 21.
Undernutrition reduced the brain growth of each group 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, respectively) and greater than that of undernourished control mice (increased 3.45-fold), whereas undernourished
IGFBP-1 Tg mice exhibited less growth (increased 3.15-fold) than undernourished control mice. When the effects of
undernutrition were examined in specific brain regions of each group, the same pattern was observed, and
IGF-I was found to be more effective in preserving the growth of the regions with the highest transgene expression (cerebral cortex, hippocampus, and diencephalon). Despite
undernutrition,
IGF-I transgene expression stimulated overgrowth of these regions as well as that of the posterior medial barrel subfield, a somatosensory area of the cerebral cortex in which
IGF-I may be especially important in development. These data indicate that
IGF-I can ameliorate the brain growth retardation caused by
undernutrition imposed during development, although it is unclear whether
IGF-I directly opposes the impact of
undernutrition or acts independently of nutritional status. Nonetheless, these findings raise the possibility that the relatively high
IGF-I expression during early postnatal life may be responsible for sparing the brain from the full impact of
undernutrition during this time in development.