| First Author | Ye P | Year | 2007 |
| Journal | J Neurosci Res | Volume | 85 |
| Issue | 4 | Pages | 712-22 |
| PubMed ID | 17279553 | Mgi Jnum | J:126403 |
| Mgi Id | MGI:3761213 | Doi | 10.1002/jnr.21181 |
| Citation | Ye P, et al. (2007) Insulin-like growth factor-I ameliorates demyelination induced by tumor necrosis factor-alpha in transgenic mice. J Neurosci Res 85(4):712-22 |
| abstractText | Our groups have reported that tumor necrosis factor-alpha (TNF-alpha) causes myelin damage and apoptosis of oligodendrocytes and their precursors in vitro and in vivo. We also have reported that insulin-like growth factor-I (IGF-I) can protect cultured oligodendrocytes and their precursors from TNF-alpha-induced damage. In this study, we investigated whether IGF-I can protect oligodendrocytes and myelination from TNF-alpha-induced damage in vivo by cross-breeding TNF-alpha transgenic (Tg) mice with IGF-I Tg mice that overexpress IGF-I exclusively in brain. At 8 weeks of age, compared with those of wild-type (WT) mice, the brain weights of TNF-alpha Tg mice were decreased by approximately 20%, and those of IGF-I Tg mice were increased by approximately 20%. The brain weights of mice that carry both TNF-alpha and IGF-I transgenes (TNF-alpha/IGF-I Tg mice) did not differ from those of WT mice. As judged by histochemical staining and immunostaining, myelin content in the cerebellum of TNF-alpha/IGF-I Tg mice was similar to that in WT mice and much more than that in TNF-alpha Tg mice. Consistently, Western immunoblot analysis showed that myelin basic protein (MBP) abundance in the cerebellum of TNF-alpha/IGF-I Tg mice was double that in TNF-alpha Tg mice. In comparison with WT mice, the number of oligodendrocytes was decreased by approximately 36% in TNF-alpha Tg mice, whereas it was increased in IGF-I Tg mice by approximately 40%. Oligodendrocyte number in TNF-alpha/IGF-I Tg mice was almost twice that in TNF-alpha Tg mice. Furthermore, IGF-I overexpression significantly reduced TNF-alpha-induced increases in apoptotic cell number, active caspase-3 abundance, and degradaion of MBP. Our results indicate that IGF-I is capable of protecting myelin and oligodendrocytes from TNF-alpha-induced damage in vivo. |
