Serum growth factors and neuroprotective surveillance: focus on IGF-1

Abstract

The adult brain requires a constant trophic input for appropriate function. Although the main source of trophic factors for mature neurons is considered to arise locally from glial cells and synaptic partners, recent evidence suggests that hormonal-like influences from distant sources may also be important. These include not only relatively well-characterized steroid hormones that cross the brain barriers, but also blood-borne protein growth factors able to cross the barriers and exert unexpected, albeit specific, trophic actions in diverse brain areas. Insulin-like growth factor I (IGF-I) is until now the serum neurotrophic factor whose actions on the adult brain are best-characterized. This is because IGF-I has been known for many years to be present in serum, whereas the presence in the circulation of other more classical neurotrophic factors has only recently been recognized. Thus, new evidence strongly suggests that IGF-I, and other blood-borne neurotrophic factors such as Fibroblast Growth Factor (FGF-2) or the neurotrophins, exert a tonic trophic input on brain cells, providing a mechanism for what we may refer to as neuroprotective surveillance. Protective surveillance includes "first-line" defense mechanisms ranging from blockade of neuronal death after a wide variety of cellular insults to upregulation of neurogenesis when defenses against neuronal death are overcome. Most importantly, surveillance should also encompass modulation of homeostatic mechanisms to prevent neuronal derangement. These will include modulation of basic cellular processes such as metabolic demands and maintainance of cell-membrane potential as well as more complex processes such as regulation of neuronal plasticity to keep neurons able to respond to constantly changing functional demands.