Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development

The in vivo actions of insulin-like growth factor-I (IGF-I) on the growth a nd development of the hippocampal dentate gyrus were investigated in transg enic mice that overexpress IGF-I postnatally in the brain and in normal non transgenic littermate controls. Stereological analyses of the dentate gyrus were performed by light and electron microscopy on days 7, 14, 21, 28, 35, and 130 to determine postnatal changes in the numerical density and total number of neurons and synapses. The volumes of both the granule cell layer and the molecular layer of the dentate gyrus were significantly increased b y 27-69% in transgenic mice after day 7, with the greatest relative increas es occurring by day 35. Although the numerical density of neurons in the gr anule cell layer did not differ significantly between transgenic and contro l mice at any age studied, the total number of neurons was significantly gr eater in transgenic mice by 29-61% beginning on day 14. The total number of synapses in the molecular layer was significantly increased by 42-105% in transgenic mice from day 14 to day 130. A transient increase in the synapse -to-neuron ratio was found in transgenic mice at postnatal days 28 and 35 b ut not at day 130. This finding indicates a disproportionate increase in sy naptogenesis, exceeding that expected for the observed increase in neuron n umber. Our results demonstrate that IGF-I overexpression produces persisten t increases in the total number of neurons and synapses in the dentate gyru s, indicating that IGF-I promotes both neurogenesis and synaptogenesis in t he developing hippocampus in vivo.