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.
Aberg
N David
ND
Department of Internal Medicine, Research Center of Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg University, Gröna Stråket 8, SE-413 45 Göteborg, Sweden. david.aberg@medic.gu.se
Johansson
Ulf E
UE
Aberg
Maria A I
MA
Hellström
Nina A K
NA
Lind
Johan
J
Bull
Cecilia
C
Isgaard
Jörgen
J
Anderson
Michelle F
MF
Oscarsson
Jan
J
Eriksson
Peter S
PS
D000367:Age Factors; D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D002196:Capillaries; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology*; D005260:Female; D007016:Hypophysectomy; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D000963:Antimetabolites; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D001973:Bromodeoxyuridine