Dataset Information

Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a new therapeutic target

ABSTRACT: Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioural 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 behavioural alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioural tests. Pharmacological enhancement of GABAergic tonic-inhibition by the FDA-approved drug ganaxolone rescued functional/behavioural alterations in mice. Establishing an unprecedented mouse model of prematurity, our work dissects the mechanisms at the core of abnormal behaviours and identifies a new, readily-translatable therapeutic strategy for preterm brain disorders.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Martina Bartolucci

LAB HEAD: Andrea Petretto

PROVIDER: PXD047704 | Pride | 2024-06-16

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20230621_093712_Plasma_Mouse_p5_p28_jb1.sne	Other
	Mouse_UP000000589.fasta	Fasta
	P5_CTRL_7_F_41.raw	Raw
	Plasma_Potenzieri.zip	Other
	Pool_CTRL_44.raw	Raw

Items per page:

1 - 5 of 47

Publications

Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target.

Potenzieri Alberto A Uccella Sara S Preiti Deborah D Pisoni Matteo M Rosati Silvia S Lavarello Chiara C Bartolucci Martina M Debellis Doriana D Catalano Federico F Petretto Andrea A Nobili Lino L Fellin Tommaso T Tucci Valter V Ramenghi Luca A LA Savardi Annalisa A Cancedda Laura L

Science advances 20240301 9

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 behav ...[more]

PMID: 38427732

Similar Datasets

Project description:Preeclampsia (PE), which affects 4-8% of human pregnancies, causes significant maternal and neonatal morbidity and mortality. Within the basal plate, placental cytotrophoblasts (CTBs) of fetal origin invade the uterus and extensively remodel the maternal vasculature. In PE, CTB invasion is often shallow, and vascular remodeling is rudimentary. To better understand possible causes, we conducted a global analysis of gene expression at the maternal-fetal interface in placental samples from women with PE (n = 12; 24-36 wk) vs. samples from women who delivered due to preterm labor with no evidence of infection (n = 11; 24-36 wk), a condition that our previous work showed is associated with normal CTB invasion. Using the HG-U133A&B Affymetrix GeneChip platform, and statistical significance set at log odds-ratio of B >0, 55 genes were differentially expressed in PE. They encoded proteins previously associated with PE [e.g. Flt-1 (vascular endothelial growth factor receptor-1), leptin, CRH, and inhibin] and novel molecules [e.g. sialic acid binding Ig-like lectin 6 (Siglec-6), a potential leptin receptor, and pappalysin-2 (PAPP-A2), a protease that cleaves IGF-binding proteins]. We used quantitative PCR to validate the expression patterns of a subset of the genes. At the protein level, we confirmed PE-related changes in the expression of Siglec-6 and PAPP-A2, which localized to invasive CTBs and syncytiotrophoblasts. Notably, Siglec-6 placental expression is uniquely human, as is spontaneous PE. The functional significance of these novel observations may provide new insights into the pathogenesis of PE, and assaying the circulating levels of these proteins could have clinical utility for predicting and/or diagnosing PE. Keywords: disease state analysis Basal plate biopsies of preterm labor (24-36 weeks; n=11) and preterm severe preeclampsia (24-36 weeeks; n=12) were isolated and the global gene expression profiles determined using Affymetrix Human GeneChips. Comparisons between the preeclampsia samples and the preterm labor controls revealed genes differentially expressed in preeclampsia.