IGF-I deficient mice show reduced peripheral nerve conduction velocities and decreased axonal diameters and respond to exogenous IGF-I treatment

Although insulin-like growth factor-I (IGF-I) can act as a neurotrophic fac tor for peripheral neurons in vitro and in vivo following injury, the role IGF-I plays during normal development and functioning of the peripheral ner vous system is unclear. Here, we report that transgenic mite with reduced l evels (two genotypes: heterozygous Igf1(+/-) or homozygous insertional muta nt Igf1(m/m)) or totally lacking IGF-I (homozygous Igf1(-/-)) show a decrea se in motor and sensory nerve conduction velocities ire vivo. In addition, A-fiber responses in isolated peroneal nerves from Igf1(+'-) and Igf1(-/-) mice are impaired. The nerve function impairment is most profound in Igf1(- 1-) mice. Histopathology of the peroneal nerves in Igf1(-1-) mice demonstra tes a shift to smaller axonal diameters but maintains the same total number of myelinated fibers as Igf1(+/+) mice. Comparisons of myelin thickness wi th axonal diameter indicate that there is no significant reduction in perip heral nerve myelination in IGF-I-deficient mice. In addition, in IGF(m/m) m ice with very low serum levels of IGF-I, replacement therapy with exogenous recombinant hIGF-I restores both motor and sensory nerve conduction veloci ties, These findings demonstrate not only that IGF-I serves an important ro le in the growth and development of the peripheral nervous system, but also that systemic IGF-I treatment can enhance nerve function in IGF-I-deficien t adult mite. (C) 1999 John Wiley & Sons, Inc.