Insulin-like growth factor-I promotes myelination of peripheral sensory axons.
Insulin-like growth factor-I (IGF-I) in vivo or in the presence of other permissive factors can promote myelination in the central nervous system. In the current study, we examine the role of IGF-I in the myelination of peripheral nerves. In rat cocultures of dorsal root ganglia (DRG) and Schwann cells (SC) grown in serum- and insulin-free defined medium, IGF-I induces a dose dependent upregulation in myelin proteins such as P0, corresponding to maximal SC ensheathment. Furthermore, IGF-I is essential in promoting a dose-dependent, long-term myelination of DRG sensory axons. In the absence of IGF-I, axons and SC survive, but fail to myelinate. In the presence of 10 nM IGF-I, 59% of axons are myelinated at 21 days, whereas in the absence of IGF-I myelination fails to occur. Maximum SC ensheathment occurs 48 hours after addition of IGF-I. If IGF-I is withdrawn at 48 hours, axon segregation by SC persists, however, most axons and SC do not exhibit a one-to-one relationship and little myelination is observed. IGF-I is important in myelination and is critical not only for initial SC ensheathment of the axon and upregulation of myelin proteins, but also for sustained myelination. Furthermore, IGF-I associated axonal size is not the sole determinant for myelination.
Russell
J W
JW
Department of Neurology, Veterans Administration Medical Center, University of Michigan, Ann Arbor 48109, USA.
Cheng
H L
HL
Golovoy
D
D
D000818:Animals; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D005727:Ganglia, Spinal / Q000166:cytology* / Q000196:embryology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008854:Microscopy, Electron; D018993:Myelin P0 Protein / Q000096:biosynthesis; D009186:Myelin Sheath / Q000187:drug effects*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D018993:Myelin P0 Protein; D007334:Insulin-Like Growth Factor I