Mutant mouse models of insulin-like growth factor actions in the central nervous system

Insulin-like growth factor-I (IGF-I) and its cognate receptor, the type 1 IGF receptor (IGF1R), as well as high-affinity IGF binding proteins (IGFBP) that modulate IGF-I actions, are expressed throughout the course of brain development. These observations, taken together with studies in cultured neu...

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Bibliographic Details
Published in:Neuropeptides (Edinburgh) 2002-04, Vol.36 (2-3), p.209-220
Main Authors: D'Ercole, Joseph A., Ye, Ping, O'Kusky, John R.
Format: Article
Language:English
Subjects:
Animals
Central Nervous System - cytology
Central Nervous System - embryology
Central Nervous System - growth & development
Central Nervous System - physiology
Female
Insulin-Like Growth Factor Binding Proteins - biosynthesis
Insulin-Like Growth Factor Binding Proteins - genetics
Insulin-Like Growth Factor I - biosynthesis
Insulin-Like Growth Factor I - genetics
Insulin-Like Growth Factor II - biosynthesis
Insulin-Like Growth Factor II - genetics
Mice
Mice, Knockout
Mutation - genetics
Neuroglia - physiology
Pregnancy
Receptor, IGF Type 1 - genetics
Somatomedins - biosynthesis
Somatomedins - genetics
Somatomedins - physiology
Synapses - physiology
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Summary:Insulin-like growth factor-I (IGF-I) and its cognate receptor, the type 1 IGF receptor (IGF1R), as well as high-affinity IGF binding proteins (IGFBP) that modulate IGF-I actions, are expressed throughout the course of brain development. These observations, taken together with studies in cultured neural cells demonstrating a variety of IGF-I growth-promoting activities, provide a strong argument for IGF-I having a central role in the growth and development of the CNS. This report reviews studies of brain development in mutant mice with alterations of IGF-I expression or action. Transgenic (Tg) mice overexpressing IGF-I postnatally exhibit brain overgrowth characterized by increased neuron and oligodendrocyte number, as well as marked increases in myelination. Mutant mice with ablated IGF-I and IGF1R expression, as well as those with overexpression of IGFBPs capable of inhibiting IGF actions, exhibit brain growth retardation with a variety of growth deficits. These studies confirm a role for IGF-I in neural development, and indicate that IGF-I stimulates neurogenesis and synaptogenesis, facilitates oligodendrocyte development, promotes neuron and oligodendrocyte survival, and stimulates myelination. Evidence from experiments in these mouse models also indicates that IGF-I has a role in recovery from neural injury.
ISSN:0143-4179
1532-2785
DOI:10.1054/npep.2002.0893