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Insulin-like growth factor 1 supplementation supports motor coordination and affects myelination in preterm pigs
Line I Christiansen1, Gemma C Ventura1, Bo Holmqvist2
1Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Insights
Postnatal insulin-like growth factor 1 (IGF-1) supplementation improved motor function in preterm pigs by enhancing brain development. This suggests potential benefits for preterm infants, though further research is needed.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Preterm infants face higher risks of neurodevelopmental impairments.
- Reduced insulin-like growth factor 1 (IGF-1) levels post-birth may contribute to these impairments.
- Preterm pigs serve as a relevant animal model for studying human preterm infant development.
Purpose of the Study:
- To investigate the effects of postnatal IGF-1 supplementation on brain development in preterm pigs.
- To determine if IGF-1 treatment can improve neurodevelopmental outcomes in this model.
Main Methods:
- Preterm pigs received either recombinant human IGF-1/IGF binding protein-3 complex or a vehicle control from birth to postnatal day 19.
- Neurofunctional assessments included motor activity, balance, gait, and cognitive tests.
- Brain analyses involved MRI, immunohistochemistry, gene expression, and protein synthesis measurements.
Main Results:
- IGF-1 supplementation increased cerebellar protein synthesis rates.
- Motor function improved in the balance beam test, but not other neurofunctional tests.
- IGF-1 reduced myelination in specific brain regions and decreased synapse formation, while enhancing GABAergic system maturation in the caudate nucleus.
Conclusions:
- Postnatal IGF-1 may support motor function in preterm neonates through enhanced GABAergic maturation, despite effects on myelination.
- Further studies are necessary to optimize IGF-1 treatment strategies for different subgroups of preterm infants.
Introduction:
Preterm infants have increased risk of impaired neurodevelopment to which reduced systemic levels of insulin-like growth factor 1 (IGF-1) in the weeks after birth may play a role. Hence, we hypothesized that postnatal IGF-1 supplementation would improve brain development in preterm pigs, used as a model for preterm infants.
Methods:
Preterm pigs delivered by cesarean section received recombinant human IGF-1/IGF binding protein-3 complex (rhIGF-1/rhIGFBP-3, 2.25 mg/kg/day) or vehicle from birth to postnatal day 19. Motor function and cognition were assessed by monitoring of in-cage and open field activities, balance beam test, gait parameters, novel object recognition and operant conditioning tests. Collected brains were subject to magnetic resonance imaging (MRI), immunohistochemistry, gene expression analyses and protein synthesis measurements.
Results:
The IGF-1 treatment increased cerebellar protein synthesis rates (both in vivo and ex vivo). Performance in the balance beam test was improved by IGF-1 but not in other neurofunctional tests. The treatment decreased total and relative caudate nucleus weights, without any effects to total brain weight or grey/white matter volumes. Supplementation with IGF-1 reduced myelination in caudate nucleus, cerebellum, and white matter regions and decreased hilar synapse formation, without effects to oligodendrocyte maturation or neuron differentiation. Gene expression analyses indicated enhanced maturation of the GABAergic system in the caudate nucleus (decreased NKCC1:KCC2 ratio) with limited effects in cerebellum or hippocampus.
Conclusion:
Supplemental IGF-1 during the first three weeks after preterm birth may support motor function by enhancing GABAergic maturation in the caudate nucleus, despite reduced myelination. Supplemental IGF-1 may support postnatal brain development in preterm infants, but more studies are required to identify optimal treatment regimens for subgroups of very or extremely preterm infants.
