Role of the growth hormone/insulin-like growth factor 1 axis in neurogenesis

Abstract

The growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is not only involved in brain growth, development and myelination, but also in brain plasticity as indexed by neurogenesis. This may have links to various cognitive effects of GH and IGF-1. GH and IGF-1 affect the genesis of neurons, astrocytes, endothelial cells and oligodendrocytes. Specifically, IGF-1 increases progenitor cell proliferation and numbers of new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In the adult cerebral cortex IGF-1 only affects oligodendrogenesis. Recently, GH therapy has also been shown to induce cell genesis in the adult brain. The profile of effects by GH therapy may be somewhat different than that of IGF-1. In addition, GH secretagogues (GHS) also have neuroprotective and cell regenerative effects per se in the brain. Finally, transgenic disruptions in GH signaling pathways affect neuron and astrocyte cell numbers during development and during adulthood. Altogether, data suggest that both exogenous and endogenous GH and/or IGF-1 may be used as agents to enhance cell genesis and neurogenesis in the adult brain. Theoretically these substances could be used to enhance recovery after brain injuries. However, further experiments with specific animal models for brain injuries are needed before clinical trials can be started.