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Insulin‐like growth factor‐I ameliorates demyelination induced by tumor necrosis factor‐α in transgenic mice
Author(s) -
Ye Ping,
Kollias George,
D'Ercole A. Joseph
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21181
Subject(s) - tumor necrosis factor alpha , endocrinology , medicine , oligodendrocyte , in vivo , immunostaining , genetically modified mouse , insulin like growth factor , myelin , biology , myelin basic protein , transgene , growth factor , chemistry , central nervous system , immunohistochemistry , receptor , biochemistry , microbiology and biotechnology , gene
Our groups have reported that tumor necrosis factor‐α (TNF‐α) 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‐α‐induced damage. In this study, we investigated whether IGF‐I can protect oligodendrocytes and myelination from TNF‐α‐induced damage in vivo by cross‐breeding TNF‐α 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‐α Tg mice were decreased by ∼20%, and those of IGF‐I Tg mice were increased by ∼20%. The brain weights of mice that carry both TNF‐α and IGF‐I transgenes (TNF‐α/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‐α/IGF‐I Tg mice was similar to that in WT mice and much more than that in TNF‐α Tg mice. Consistently, Western immunoblot analysis showed that myelin basic protein (MBP) abundance in the cerebellum of TNF‐α/IGF‐I Tg mice was double that in TNF‐α Tg mice. In comparison with WT mice, the number of oligodendrocytes was decreased by ∼36% in TNF‐α Tg mice, whereas it was increased in IGF‐I Tg mice by ∼40%. Oligodendrocyte number in TNF‐α/IGF‐I Tg mice was almost twice that in TNF‐α Tg mice. Furthermore, IGF‐I overexpression significantly reduced TNF‐α‐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‐α‐induced damage in vivo. © 2007 Wiley‐Liss, Inc.