Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs
(2023) In eNeuro 10(4).- Abstract
Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurode-velopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investi-gated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was measured using in vivo... (More)
Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurode-velopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investi-gated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was measured using in vivo labeling with [2H5] phenylalanine. We showed that the IGF-1 receptor was widely distributed in the brain and largely coexisted with immature neurons. Region-spe-cific quantification of IHC labeling showed that IGF-1 treatment promoted neuronal differentiation, increased subcorti-cal myelination, and attenuated synaptogenesis in a region-dependent and time-dependent manner. The expression levels of genes involved in neuronal and oligodendrocyte maturation, and angiogenic and transport functions were al-tered, reflecting enhanced brain maturation in response to IGF-1 treatment. Cerebellar protein synthesis was increased by 19% at day 5 and 14% at day 9 after IGF-1 treatment. Treatment had no effect on Iba1+ microglia or regional brain weights and did not affect motor development or the expression of genes related to IGF-1 signaling. In conclusion, the data show that supplemental IGF-1 promotes brain maturation in newborn preterm pigs. The results provide further support for IGF-1 supplementation therapy in the early postnatal period in preterm infants.
(Less)
- author
- organization
- publishing date
- 2023-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cortex, developing brain, hippocampus, IGF-1, IGF1R
- in
- eNeuro
- volume
- 10
- issue
- 4
- article number
- ENEURO.0430-22.2023
- publisher
- Society for Neuroscience
- external identifiers
-
- pmid:36973010
- scopus:85152405731
- ISSN
- 2373-2822
- DOI
- 10.1523/ENEURO.0430-22.2023
- language
- English
- LU publication?
- yes
- id
- a45674e2-65e6-4266-b7c1-57da1cffa2b1
- date added to LUP
- 2023-07-14 09:25:55
- date last changed
- 2024-04-19 23:25:34
@article{a45674e2-65e6-4266-b7c1-57da1cffa2b1,
abstract = {{<p>Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurode-velopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investi-gated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development. Pigs were treated with 2.25 mg/kg/d recombinant human IGF-1/IGF binding protein-3 complex from birth until day 5 or 9 before the collection of brain samples for quantitative immunohistochemistry (IHC), RNA sequencing, and quantitative PCR analyses. Brain protein synthesis was measured using in vivo labeling with [2H5] phenylalanine. We showed that the IGF-1 receptor was widely distributed in the brain and largely coexisted with immature neurons. Region-spe-cific quantification of IHC labeling showed that IGF-1 treatment promoted neuronal differentiation, increased subcorti-cal myelination, and attenuated synaptogenesis in a region-dependent and time-dependent manner. The expression levels of genes involved in neuronal and oligodendrocyte maturation, and angiogenic and transport functions were al-tered, reflecting enhanced brain maturation in response to IGF-1 treatment. Cerebellar protein synthesis was increased by 19% at day 5 and 14% at day 9 after IGF-1 treatment. Treatment had no effect on Iba1<sup>+</sup> microglia or regional brain weights and did not affect motor development or the expression of genes related to IGF-1 signaling. In conclusion, the data show that supplemental IGF-1 promotes brain maturation in newborn preterm pigs. The results provide further support for IGF-1 supplementation therapy in the early postnatal period in preterm infants.</p>}},
author = {{Christiansen, Line I. and Holmqvist, Bo and Pan, Xiaoyu and Holgersen, Kristine and Lindholm, Sandy E.H. and Henriksen, Nicole L. and Burrin, Douglas G. and Ley, David and Thymann, Thomas and Sangild, Per Torp and Pankratova, Stanislava}},
issn = {{2373-2822}},
keywords = {{cortex; developing brain; hippocampus; IGF-1; IGF1R}},
language = {{eng}},
number = {{4}},
publisher = {{Society for Neuroscience}},
series = {{eNeuro}},
title = {{Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs}},
url = {{http://dx.doi.org/10.1523/ENEURO.0430-22.2023}},
doi = {{10.1523/ENEURO.0430-22.2023}},
volume = {{10}},
year = {{2023}},
}