Protective and regenerative effects of the GH/IGF-I axis on the brain

Apart from regulating somatic growth and metabolism, evidence suggest that the GH/ IGF-I axis is involved in the regulation of brain growth, development and myelination. Moreover, growth hormone (GH) and particularly IGF-I have been attributed neuroprotective effects in different in vitro and in vivo experimental models. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are suggested to be mediated by circulating IGF-I, while other effects may be due to locally produced IGF-I within the brain. It is also possible that GH may act directly on the central nervous system (CNS) without involving IGF-I (either circulating or locally). Plasticity in the CNS may be viewed as changes in the functional interplay between the major cell types neurons, astrocytes and oligodendrocytes. GH and IGF-I affect all these cell types in several aspects. Apart from neuroprotective effects of GH and IGF-I in different experimental models of CNS injury, IGF-I has been found to increase progenitor cell proliferation and new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In the adult cerebral cortex, it appears that only oligodendrogenesis is affected. The increase of IGF-I on endothelial cell phenotype may explain the increase in cerebral arteriole density observed after GH treatment. In the present review, different aspects of the GH/IGF-I axis effects on the brain will be discussed with particular emphasis on neuroprotection, regeneration and brain plasticity. Moreover, recent findings describing neuroprotective effects and effects on synaptic plasticity by GH secretagogues will be reviewed.