The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Circulating Insulin-Like Growth Factor I Mediates Exercise-Induced Increases in the Number of New Neurons in the Adult Hippocampus
Open accessAbstract
Although the physiological significance of continued formation of new neurons in the adult mammalian brain is still uncertain, therapeutic strategies aimed to potentiate this process show great promise. Several external factors, including physical exercise, increase the number of new neurons in the adult hippocampus, but underlying mechanisms are not yet known. We recently found that exercise stimulates uptake of the neurotrophic factor insulin-like growth factor I (IGF-I) from the bloodstream into specific brain areas, including the hippocampus. In addition, IGF-I participates in the effects of exercise on hippocampal c-fos expression and mimics several other effects of exercise on brain function. Because subcutaneous administration of IGF-I to sedentary adult rats markedly increases the number of new neurons in the hippocampus, we hypothesized that exercise-induced brain uptake of blood-borne IGF-I could mediate the stimulatory effects of exercise on the adult hippocampus. Thus, we blocked the entrance of circulating IGF-I into the brain by subcutaneous infusion of a blocking IGF-I antiserum to rats undergoing exercise training. The resulting inhibition of brain uptake of IGF-I was paralleled by complete inhibition of exercise-induced increases in the number of new neurons in the hippocampus. Exercising rats receiving an infusion of nonblocking serum showed normal increases in the number of new hippocampal neurons after exercise. Thus, increased uptake of blood-borne IGF-I is necessary for the stimulatory effects of exercise on the number of new granule cells in the adult hippocampus. Taken together with previous results, we conclude that circulating IGF-I is an important determinant of exercise-induced changes in the adult brain.
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In the citing paper
“Other researchers have reported exercise-related increased productions of other neurotrophic factors such as insulin-like growth factor 1 and vascular endothelial growth factor, which have been linked with angiogenesis (the growth of new vasculature) and neurogenesis”
From Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? (2008) · cites this paper as Trejo, Carro, & Torres-Aleman, 2001
Experimental — accuracy not yet measuredIn the citing paper
“Factors including IGF-1 (ref. 9), VEGF10 and PF4 (ref.11) increase hippocampal neurogenesis in young mice”
From Exercise plasma boosts memory and dampens brain inflammation via clusterin (2021) · cites this paper as [9]
In the citing paper
“Like BDNF, the levels of IGF-1 increase in the circulation in response to physical activity (521)”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [521]
In the citing paper
“and both exercise and systemic infusion of IGF-1 increases new and survivability of BrdU+ cells in the hippocampus (323, 521), likely signaling through IGF-receptors located on the luminal side of the brain (323).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [521]
In the citing paper
“Specifically, treadmill exercises in rats increase cell proliferation via insulin-like growth factor-1 (Trejo et al., 2001) and cell proliferation and survival in the dentate gyrus (van Praag, Kempermann, & Gage, 1999b).”
From The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD? (2011) · cites this paper as Trejo et al., 2001
In the citing paper
“It has been demonstrated in animal models that AE stimulates the sprouting of new capillaries (angiogenesis) and improves vasculature within the hippocampus (Trejo et al., 2001; van Praag et al., 2005).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Trejo et al., 2001
In the citing paper
“Indeed, the inhibition of VEGF or IGF-1 has been demonstrated to impair the promotional impact of AE on the rate of neurogenesis (Trejo et al., 2001; Fabel et al., 2003; Ding et al., 2006) and spatial memory performance (Ding et al., 2006).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Trejo et al., 2001
In the citing paper
“Conversely, up-regulating either VEGF or IGF-1 can stimulate neurogenesis independently of AE (Aberg et al., 2000; Carro et al., 2000; Trejo et al., 2001; Cao et al., 2004).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Trejo et al., 2001
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Citations
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Learning enhances adult neurogenesis in the hippocampal formation
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Normal growth and development in the absence of hepatic insulin-like growth factor I
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Ageing, fitness and neurocognitive function
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Induction of neurogenesis in the neocortex of adult mice
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Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat
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Physiology and neurobiology of stress and adaptation: central role of the brain
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Be smart, exercise your heart: Exercise effects on brain and cognition
Hillman, C. H., Erickson, K. I., & Kramer, A. F. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2298 · Cited by 3,563
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Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575
Ross, R., Blair, S. N., Arena, R., Church, T. S., Després, J.-P., Franklin, B. A., Haskell, W. L., Kaminsky, L. A., Levine, B. D., Lavie, C. J., et al. (2016) · Circulation · doi:10.1161/cir.0000000000000461 · Cited by 2,486
Metadata
- Authors
- Trejo, J. L., Carro, E., & Torres-Alemán, I.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- ORCID
- Carro, Eva
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-03-01
- Volume
- 21
- Issue
- 5
- Pages
- 1628-1634
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762955
- OpenAlex
- W2136855986
- Cited by
- 1,017
- References
- 47
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 25 · 2023: 30 · 2022: 34 · 2021: 40 · 2020: 42 · 2019: 48 · 2018: 34 · 2017: 48 · 2016: 50 · 2015: 52 · 2014: 54 · 2013: 45 · 2012: 57
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- insulin-like growth factor I, physical activity, adult hippocampus, adult neurogenesis, granule cells, Fos expression, neurotrophic factors
- MeSH terms
- Animals, Blood-Brain Barrier, Bromodeoxyuridine, Cell Count, Cell Division, Physical Exertion, Hippocampus, Immune Sera, Immunohistochemistry, Insulin-Like Growth Factor I, Male, Neurons, Phenotype, Rats, Wistar, Rats
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