The role of the insulin-like growth factor system in the developing brain.
Insulin-like growth factors (IGFs) play a central role in brain growth and development, with IGF-1, its receptors and binding proteins (IGFBPs) being highly expressed, particularly in the olfactory bulb (OB), representing a local paracrine system. A potential role of IGFBPs in transporting and targeting IGFs to their receptors is supported by the finding that abundant IGFBP-2 is associated with cell surface proteoglycans. An OB organ culture system expressing IGF-1 and IGFBPs represents an in vitro injury model. Although IGF-1 is potently antiapoptotic for neurons and oligodendrocytes, marked gliosis and IGFBP-3 expression are seen, similar to in vivo injury responses, where intraventricular injection of IGF-1 postinjury enhances neuronal survival by blocking apoptosis. In contrast, des (1-3) IGF-1, which has low affinity for IGFBPs, is ineffective, supporting a transport or receptor targeting role for local IGFBPs. We conclude that the IGF system plays a crucial cell survival and growth role in the developing and injured brain and that IGFs have significant therapeutic potential.
Werther
G A
GA
Centre for Hormone Research, Royal Children's Hospital, Parkville, Vic., Australia.
Russo
V
V
Baker
N
N
Butler
G
G
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000254:growth & development*; D001930:Brain Injuries; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D009830:Olfactory Bulb; D009924:Organ Culture Techniques; D013002:Somatomedins / Q000502:physiology*
D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I