Peripheral Infusion of Insulin-Like Growth Factor-I Increases the Number of Newborn Oligodendrocytes in the Cerebral Cortex of Adult Hypophysectomized Rats

Abstract

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.

17β‐estradiol and progesterone prevent cuprizone provoked demyelination of corpus callosum in male mice

“…The recruitment of new oligodendrocytes could be the result of stimulated astrogliosis and, subsequently, IGF-1 synthesis and release by astrocytes as observed in our study. IGF-1 is important for oligodendrocyte differentiation, maturation, and myelin formation but also can interact with mature oligodendrocytes thereby preventing cell death under different toxic conditions (Aberg et al, 2007;Cui and Almazan 2007;Darlington 2005;Salmaso and Woodside 2008). It is wellestablished that IGF-1 and sex steroids are interconnected in the brain.…”

Insulin-like Growth Factor System Regulates Oligodendroglial Cell Behavior: Therapeutic Potential in CNS

“…After IGF-1 administration in adult hypophysectomized rats, it was shown that the number of BrdU-labeled oligodendrocyte progenitor cells in the cerebral cortex after 6 days did not increase, whereas after 20 days, BrdU-positive OPC population did increase (Aberg et al 2007). Authors concluded that as IGF-1 did not substantially induce cortical progenitor cell proliferation after 6 days, BrdUpositive cells observed at day 20 must have been derived from increased BrdU-negative OPC populations at an earlier stage, and that this increase reflects IGF-mediated enhanced survival of newborn cells.…”

Peripheral growth hormone induces cell proliferation in the intact adult rat brain

“…In adult hypophysectomized rats both GH [8] and IGF-I [9][10][11] increase cell genesis in several brain regions. These may be direct effects, since both factors are able to cross the blood-brain barrier and bind to receptors that are distributed throughout the brain (reviewed in [1]), or indirect effects that are related to circulating IGF-I, since GH elevates the serum level of IGF-I [12].…”