Insulin-Like Growth Factor-I Promotes Neurogenesis and Synaptogenesis in the Hippocampal Dentate Gyrus during Postnatal Development

Abstract

The in vivo actions of insulin-like growth factor-I (IGF-I) on the growth and development of the hippocampal dentate gyrus were investigated in transgenic mice that overexpress IGF-I postnatally in the brain and in normal nontransgenic 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 by 27-69% in transgenic mice after day 7, with the greatest relative increases occurring by day 35. Although the numerical density of neurons in the granule cell layer did not differ significantly between transgenic and control mice at any age studied, the total number of neurons was significantly greater 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 but not at day 130. This finding indicates a disproportionate increase in synaptogenesis, exceeding that expected for the observed increase in neuron number. Our results demonstrate that IGF-I overexpression produces persistent increases in the total number of neurons and synapses in the dentate gyrus, indicating that IGF-I promotes both neurogenesis and synaptogenesis in the developing hippocampus in vivo.

IGF‐1 receptor‐mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus

“…With respect to IGF-1, a number of studies have shown that circulating levels of IGF-1 stimulate proliferation (Aberg et al, 2000;Trejo et al, 2001). In addition, IGF-1 overexpression promotes neurogenesis and synaptogenesis in the dentate gyrus and IGF-1 knock out mouse exhibit a reduction in granule cell numbers (Beck et al, 1995;O'Kusky et al, 2000). Furthermore, Ziv et al (2006) reported that environmental enrichment-induced neurogenesis in the hilus correlates with hilar microglial activation and IGF-1 expression.…”

Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart

“…Given that insulin and insulin-like factors not only protect brain tissue, but also favor processes such as neurogenesis and synaptogenesis (O'Kusky et al, 2000;van der Heide et al, 2005), and on the background of reduced CNS expression of genes encoding insulin and related messengers in patients suffering from AD (Steen et al, 2005), this outcome may be of considerable relevance for future clinical applications of insulin compounds in the treatment of memory disorders.…”

Neural control of aging skeletal muscle

“…In young animals, systemic administration of IGF-1 decreases lesion-induced motor neurone cell death and promotes muscle re-innervation (Vergani et al, 1998). IGF-1 also promotes neurogenesis and synaptogenesis in diverse areas of the central nervous system such as the hypocampal dentate gyrus during postnatal development (O'Kusky et al, 2000) or increases proliferation of granule cell progenitors (Ye et al, 1996). These studies suggest that IGF-1 might have beneficial effects on spinal cord motor neurones from senescent mammals.…”