Insulin-like growth factor 1 supplementation supports motor coordination and affects myelination in preterm pigs.

Autor:	Christiansen LI; Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Ventura GC; Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Holmqvist B; ImaGene-iT AB, Lund, Sweden., Aasmul-Olsen K; Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Lindholm SEH; Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Lycas MD; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Mori Y; Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Secher JB; Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Burrin DG; United States Department of Agriculture, Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States., Thymann T; Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark., Sangild PT; Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.; Department of Neonatology, Rigshospitalet, Copenhagen, Denmark.; Department of Pediatrics, Odense University Hospital, Odense, Denmark.; Faculty of Theology, University of Copenhagen, Copenhagen, Denmark., Pankratova S; Comparative Pediatrics and Nutrition, Department of Veterinary and Animals Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.; Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in neuroscience [Front Neurosci] 2023 Jun 19; Vol. 17, pp. 1205819. Date of Electronic Publication: 2023 Jun 19 (Print Publication: 2023).
DOI:	10.3389/fnins.2023.1205819
Abstrakt:	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. Competing Interests: BH was employed by ImaGene-iT AB. The University of Copenhagen represented by authors TT, PS, and SP, and the company Oak Hill Bio have filed a patent application directed to use of rhIGF-1 for preterm infants. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Christiansen, Ventura, Holmqvist, Aasmul-Olsen, Lindholm, Lycas, Mori, Secher, Burrin, Thymann, Sangild and Pankratova.)
Databáze:	MEDLINE
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