Abstract
IGF-I and IGF-II are ubiquitously expressed growth factors that have profound effects on the growth and differentiation of many cell types and tissues, including cells of the CNS. In biologic fluids, most IGFs are bound to one of six IGF binding proteins (IGFBPs 1–6). Increasing evidence strongly supports a role for IGF-I in CNS development, as it promotes neuronal proliferation and survival. However, little is known about IGF-I and its homolog IGF-II and their carrier proteins, IGFBPs, during the neonatal period in which brain size increases dramatically, myelination takes place, and neurons show limited capacity to proliferate. Herein, we have determined the concentrations of IGF-I, IGF-II, IGFBP-1, and IGFBP-3 in cerebral spinal fluid (CSF) samples that were collected from children who were 1 wk to 18 y of age. The concentrations of IGF-I, IGFBP-1, and IGFBP-3 in CSF from children <6 mo of age were significantly higher than in older children, whereas IGF-II was higher in the older group. This is in contrast to what is observed in the peripheral circulation, where IGF-I and IGFBP-3 are low at birth and rise rapidly during the first year, reaching peak levels during puberty. Higher concentrations of IGF-I, IGFBP-1, and IGFBP-3 in the CSF of very young children suggest that these proteins might participate in the active processes of myelination and synapse formation in the developing nervous system. We propose that IGF-I and certain IGFBPs are likely necessary for normal CNS development during critical stages of neonatal brain growth and development.
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Abbreviations
- CSF:
-
cerebrospinal fluid
- IGFBP:
-
IGF binding protein
- IGFR:
-
IGF receptor
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Acknowledgements
We thank Beverly Word and Joanie Barnett for technical assistance in performing assays and collecting patient samples. We also thank Dr. Susan Durham for advice while conducting these studies and Diagnostic Systems Laboratories for provision of the assay kits used in this study.
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This work was supported in part by National Institutes of Health Grant R01DK055653 (J.L.F), the Genentech Center for Clinical Research and Education (M.K.W.), National Institutes of Health Grant C06 RR16517 to Arkansas Children's Hospital Research Institute and the Arkansas Biosciences Institute (R.C.B. and J.L.F.).
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Bunn, R., King, W., Winkler, M. et al. Early Developmental Changes in IGF-I, IGF-II, IGF Binding Protein-1, and IGF Binding Protein-3 Concentration in the Cerebrospinal Fluid of Children. Pediatr Res 58, 89–93 (2005). https://doi.org/10.1203/01.PDR.0000156369.62787.96
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DOI: https://doi.org/10.1203/01.PDR.0000156369.62787.96
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