Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs. / Christiansen, Line I.; Holmqvist, Bo; Pan, Xiaoyu; Holgersen, Kristine; Lindholm, Sandy E.H.; Henriksen, Nicole L.; Burrin, Douglas G.; Ley, David; Thymann, Thomas; Sangild, Per Torp; Pankratova, Stanislava.
In: eNeuro, Vol. 10, No. 4, ENEURO.0430-22.2023, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs
AU - Christiansen, Line I.
AU - Holmqvist, Bo
AU - Pan, Xiaoyu
AU - Holgersen, Kristine
AU - Lindholm, Sandy E.H.
AU - Henriksen, Nicole L.
AU - Burrin, Douglas G.
AU - Ley, David
AU - Thymann, Thomas
AU - Sangild, Per Torp
AU - Pankratova, Stanislava
N1 - Publisher Copyright: © 2023 Christiansen et al.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - cortex
KW - developing brain
KW - hippocampus
KW - IGF-1
KW - IGF1R
U2 - 10.1523/ENEURO.0430-22.2023
DO - 10.1523/ENEURO.0430-22.2023
M3 - Journal article
C2 - 36973010
AN - SCOPUS:85152405731
VL - 10
JO - eNeuro
JF - eNeuro
SN - 2373-2822
IS - 4
M1 - ENEURO.0430-22.2023
ER -
ID: 345423824