| First Author | Potenzieri A | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 9 | Pages | eadk8123 |
| PubMed ID | 38427732 | Mgi Jnum | J:359384 |
| Mgi Id | MGI:7609430 | Doi | 10.1126/sciadv.adk8123 |
| Citation | Potenzieri A, et al. (2024) Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target. Sci Adv 10(9):eadk8123 |
| abstractText | 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. |
