IN-VIVO EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON THE DEVELOPMENT OFSENSORY PATHWAYS - ANALYSIS OF THE PRIMARY SOMATIC SENSORY CORTEX (S1) OF TRANSGENIC MICE

In the rodent brain, insulin like growth factor I(IGF-I) messenger RNA is transiently expressed in sensory projection neurons during periods of synaptogenesis and neuronal growth. Transgenic (Tg) mice with brai n IGF-I overexpression and ectopic brain expression of IGF-binding pro tein-1 (IGFBP-1), an inhibitor of IGF-I actions, show changes in brain size and myelination. We used these mouse models to evaluate in vivo IGF-I effects on sensory pathway development by conducting anatomical studies in the Si barrel field. Brain size, cortical area, and barrel field dimensions were increased in IGF-I and reduced in IGFBP-1 Tg mic e compared with those in wild-type (wt) mice. The brain and cerebral c ortex of Tg mice with the highest transgene expression were the most a ltered in size. Cortex and barrel field size changes were not precisel y proportional, because in some Tg mice barrels were relatively more a ffected than the cortex, whereas in others the opposite was observed. Brain IGF-I overexpression increased the average number of neurons per barrel, neuronal cell body cross-sectional area, and barrel neuropil volume, whereas brain expression of IGFBP-1 reduced each. Neuronal den sity was greatly reduced in IGF-I Tg mice and increased in IGFBP-1 Tg mice. No differences in body weight, whisker pad and follicle areas, a nd whisker pad innervation density were found among Tg and wt mice. Th ese observations indicate that IGF-I enhances neuronal growth in devel oping sensory pathways and support the concept: that modified availabi lity of local trophic factors, such as IGF-I, changes brain, neocortic al, and S1 relative dimensions by altering neuronal survival and neuro pil elaboration. Study of the Si cortex provides an excellent model to probe the in vivo mechanisms of IGF actions.