Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target
Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcom...
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| Veröffentlicht in: | Science advances 2024-03, Vol.10 (9), p.eadk8123-eadk8123 |
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| creator | Potenzieri, Alberto Uccella, Sara Preiti, Deborah Pisoni, Matteo Rosati, Silvia Lavarello, Chiara Bartolucci, Martina Debellis, Doriana Catalano, Federico Petretto, Andrea Nobili, Lino Fellin, Tommaso Tucci, Valter Ramenghi, Luca A Savardi, Annalisa Cancedda, Laura |
| description | Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcomes. Here, we mimicked IGF-1 deficiency of preterm newborns in mice by perinatal administration of an IGF-1 receptor antagonist. This resulted in sex-biased brain microstructural, functional, and behavioral alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioral tests. Pharmacological enhancement of GABAergic tonic inhibition by the U.S. Food and Drug Administration-approved drug ganaxolone rescued functional/behavioral alterations in mice. Establishing an unprecedented mouse model of prematurity, our work dissects the mechanisms at the core of abnormal behaviors and identifies a readily translatable therapeutic strategy for preterm brain disorders. |
| doi_str_mv | 10.1126/sciadv.adk8123 |
| format | Article |
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Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcomes. Here, we mimicked IGF-1 deficiency of preterm newborns in mice by perinatal administration of an IGF-1 receptor antagonist. This resulted in sex-biased brain microstructural, functional, and behavioral alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioral tests. Pharmacological enhancement of GABAergic tonic inhibition by the U.S. Food and Drug Administration-approved drug ganaxolone rescued functional/behavioral alterations in mice. 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| subjects | Animals Brain Diseases - drug therapy Child Female Humans Infant, Newborn Infant, Premature Insulin-Like Growth Factor I Mice Placenta Pregnancy Receptor, IGF Type 1 United States |
| title | Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target |
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