Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs
Related Experiment Video
Updated: Aug 5, 2025
Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
Line I Christiansen1, Bo Holmqvist2, Xiaoyu Pan1
1Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
Insights
Supplemental insulin-like growth factor-1 (IGF-1) promotes brain maturation in preterm pigs. This study suggests IGF-1 therapy may improve neurodevelopment in preterm infants.
Area of Science:
- Neonatal Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Very preterm infants have low insulin-like growth factor-1 (IGF-1) levels, linked to poor growth and neurological outcomes.
- The impact of IGF-1 supplementation on neurodevelopment in preterm neonates is not well understood.
Purpose of the Study:
- To investigate the effects of supplemental IGF-1 on brain development and motor function in preterm pigs, a model for preterm infants.
- To determine if IGF-1 promotes neuronal differentiation, myelination, and synaptogenesis.
Main Methods:
- Preterm pigs received recombinant human IGF-1/IGF binding protein-3 complex from birth.
- Brain tissue was analyzed using quantitative immunohistochemistry, RNA sequencing, and qPCR.
- In vivo protein synthesis was measured using phenylalanine labeling.
Main Results:
- IGF-1 treatment promoted neuronal differentiation and subcortical myelination in a region- and time-dependent manner.
- Gene expression analysis indicated enhanced brain maturation, including neuronal and oligodendrocyte development.
- Cerebellar protein synthesis increased significantly post-IGF-1 treatment, with no adverse effects on microglia or motor development.
Conclusions:
- Supplemental IGF-1 effectively promotes brain maturation in newborn preterm pigs.
- These findings support the potential of IGF-1 supplementation therapy for improving early postnatal neurodevelopment in preterm infants.
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 neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated 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-specific quantification of IHC labeling showed that IGF-1 treatment promoted neuronal differentiation, increased subcortical 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 altered, 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.
