Peripheral infusion of insulin-like growth factor-I increases the number of newborn oligodendrocytes in the cerebral cortex of adult hypophysectomized rats

We have previously shown that recombinant human( rh) IGF- I induces cell proliferation and neurogenesis in the hippocampus of hypophysectomized rats. In the current investigation, we determined the effects of rhIGF- I on proliferation and differentiation in the cerebral cortex. Adult hypophysectomized rats were injected with bromodeoxyuridine ( BrdU) to label newborn cells ( once a day for the first 5 d), and rhIGF- I was administered peripherally for 6 or 20 d. In the cerebral cortex, the number of BrdU- labeled cells increased after 20 d but not after 6 d of rhIGF- I infusion. This suggests that rhIGF- I enhances the survival of newborn cells in the cerebral cortex. Using BrdU labeling combined with the oligodendrocyte- specific markers myelin basic protein and 2', 3'- cyclic nucleotide 3'- phosphodiesterase, we demonstrated an increase in oligodendrogenesis in the cerebral cortex. The total amount of myelin basic protein and 2', 3'- cyclic nucleotide 3'- phosphodiesterase was also increased on Western blots of homogenates of the cerebral cortex, confirming the immunohistochemical findings. Also, we observed an increase in the number of capillary- associated BrdU- positive cells, although total capillary area was not increased. rhIGF- I treatment did not affect cortical astrogliogenesis and neurogenesis was not observed. The ability of rhIGF- I to induce cortical oligodendrogenesis may have implications for the regenerative potential of the cortex.