IGF-I and postnatal growth in neurodegenerative diseases
Insulin-like growth factor I (IGF-I) is an anabolic growth factor essential for growth and development, both as a mediator of growth hormone action (GH) and as a local stimulator of cell proliferation and differentiation. Although the importance of IGF-I in postnatal growth has been established, the consequences of its deficiency in several neurodegenerative diseases have not been studied. The weaver mutant mouse, a commonly used model for studying hereditary cerebellar ataxia, provides an opportunity to study the function of IGF-I in postnatal growth and during neurodegeneration. Compared to their normal littermates, we found a parallel decrease of body growth and circulating IGF-I levels in weaver mice. We also found that both abnormalities can be corrected by overexpressing an IGF-I transgene. Weaver mice carrying an IGF-I transgene not only increased their circulating IGF-I levels, but also restored their body weights and normalized their bone growth and body composition. Alternatively, the same normalization can be achieved by supplementing GH to weaver mice, which also have reduced circulating GH levels but have normal hepatic GH receptor function. In summary, our studies demonstrate that GH/IGF-l axis plays an important role in normal postnatal growth as well as in neurodegenerative diseases. Because decreased circulating IGF-I levels are associated with neurodegenerative diseases and brain injury, our results strongly support IGF-I's clinical benefit for patients who suffer these debilitating conditions.