Circulating insulin-like growth factor I and cognitive function: neuromodulation throughout the lifespan.

Insulin-like growth factor I (IGF-I) is central to the somatotropic (growth hormone) axis. It promotes tissue growth and continues to have anabolic effects in adulthood. Accumulating evidence from the last decade, however, reveals that circulating levels of IGF-I also significantly affects cognitive brain function. Specifically, the decline of serum IGF-I might be associated with the age-related cognitive decline in elderly people. Moreover, psychiatric and neurological conditions characterized by cognitive impairment may be characterized by altered levels of IGF-I. Some evidence is emerging that interventions that target the GH/IGF-I axis may improve cognitive functioning, at least in deficient states. As there is evidence linking high serum IGF-I levels with cancer risk, these interventions should be carefully evaluated. On a cellular and molecular level, IGF-I may be a crucial component of neural homeostasis since disturbed IGF-I input is inevitably linked to perturbed function. Consistent with this, all nerve cells are potential targets of IGF-I actions, including neurons, glia, endothelial, epithelial, and perivascular cells. Indeed, many key cellular processes in the brain are affected by IGF-I's neurotrophic and modulatory actions. We review the regulation by IGF-I of neurotransmission and neuronal plasticity and conclude that serum IGF-I is an important mediator of neuronal growth, survival and function throughout the lifespan. The role of IGF-I in synaptic plasticity render its neurotrophic potential a key target for remediating the cognitive impairment associated with a range of neurological conditions.