Insulin-Like Growth Factor-I Promotes Neurogenesis and Synaptogenesis in the Hippocampal Dentate Gyrus during Postnatal Development
Open accessAbstract
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.
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IGF-1 is important in hippocampal neurogenesis and synaptogenesis in mice.
“Developmental research in mice has revealed the importance of IGF-1 in hippocampal neurogenesis and synaptogenesis (O’Kusky et al. 2000).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as O’Kusky et al. 2000
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- Authors
- O'Kusky, J. R., Ye, P., & D'Ercole, A. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Ye, Ping
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-11-15
- Volume
- 20
- Issue
- 22
- Pages
- 8435-8442
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6773150
- OpenAlex
- W1864437270
- Cited by
- 358
- References
- 4
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 8 · 2023: 13 · 2022: 15 · 2021: 7 · 2020: 12 · 2019: 9 · 2018: 11 · 2017: 12 · 2016: 22 · 2015: 23 · 2014: 17 · 2013: 17 · 2012: 17
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Rick Hansen Institute
- Medical Research Council Canada
- National Institutes of Health
- Medical Research Council
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 08299, R01HD008299)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- insulin-like growth factor I, neurogenesis, synaptogenesis, dentate gyrus, hippocampus, postnatal brain development, transgenic mice, neuron number, synapse number, granular layer, molecular layer, neuronal growth factors
- MeSH terms
- Analysis of Variance, Animals, Body Weight, Cell Count, Cerebellum, Cerebral Cortex, Diencephalon, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Mice, Transgenic, Neurons, Organ Size, Synapses, Telencephalon, Dentate Gyrus, Mice
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