Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus

By M. Åberg, N. Åberg, Helena Hedbäcker, J. Oscarsson, P. Eriksson. Journal of Neuroscience, 2000

867 citations recorded by the source corpus.

In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdU-immunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D28K, microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 ± 17% (p < 0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Endocrinology, Diabetes and Metabolism

View Paper: https://www.semanticscholar.org/paper/cf56bb3d96435f2937141ebd8306692abdf5b03a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Duman
2. Bruce S. McEwen
3. H. van Praag
4. Fred H. Gage
5. E. Nestler
6. M. Le Moal
7. H. Schmidt
8. D. Abrous

In Developmental Neuroscience

1. R. Duman
2. Fred H. Gage
3. H. van Praag
4. Bruce S. McEwen
5. D. Abrous
6. H. Schmidt
7. M. Le Moal
8. E. Nestler

In Endocrinology, Diabetes and Metabolism

1. Bruce S. McEwen
2. H. van Praag
3. R. Duman
4. J. Trejo
5. H. Schmidt
6. I. Torres-Alemán
7. E. Carro
8. J. Wingfield

Citations in the corpus

• Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. (2002, background): “Circulating IGF-1 is another stimulator of neurogenesis [1,140].”
• Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. (2002, positive): “…5.3 mm and lateral 1.2administrations of FGF-2 and IGF-I have been shown to mm with cannula depth 3.3 mm below the surface of the dura matter. stimulate neurogenesis in the adult hippocampus The morphology of neuronal cell body and synapses was examined (Wagner et al., 1999; Åberg et al., 2000).”
• Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus (2000, background): “IGF-1 increases proliferation and survival of neurons in adult rat (Aberg et al., 2000), although antidepressant regulation of this factor has not been demonstrated.”
• Progesterone receptors: form and function in brain. (2008, positive): “Age-associated decline in neurogenic potential in the dentate gyrus has been observed as early as middle age [159,220] and has been proposed to contribute to age-related learning and memory impairments [62,84,89,1].”
• Adult neurogenesis: from precursors to network and physiology. (2005, background): “Its influence on neurogenesis has been examined in hypophysiectomized rats presenting low levels of circulating IGF-I (1).”
• Physiology and neurobiology of stress and adaptation: central role of the brain. (2007, background): “Circulating IGF-I is a key mediator of the ability of physical activity to increase neurogenesis in the dentate gyrus of the hippocampal formation (1, 48).”
• Exercise and the brain: something to chew on (2009, background): “Hippocampal gene transfer of VEGF [77] and peripheral infusion of IGF-1 enhanced neurogenesis [78].”
• The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Signals regulating adult hippocampal neurogenesis Stages Regulators Secreted factors and downstream effectors (Morphogens, growth fa”