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Dose- and sex-dependent effects of phlebotomy-induced anemia on inflammation and neurodevelopment in the neonatal mouse hippocampus

ABSTRACT: Phlebotomy-induced anemia (PIA) is universal and highly variable in degree among preterm infants. PIA contributes to the preterm infant’s considerable neurodevelopmental risk. In the mouse, neonatal PIA causes brain tissue hypoxia and iron deficiency accompanied by long-term sex-dependent neurobehavioral abnormalities. The neuroregulatory pathways disrupted by PIA underlying these effects are unknown. This study determined the effects of PIA severity and sex on the hippocampal transcriptome of young mice. ). NGS data from mPIA females showed the least DEGs (0.5% of >22,000 genes) whereas sPIA females had the most (8.6%), indicating a dose-dependent effect. Conversely, mPIA and sPIA males showed similar changes in gene expression (5.3% and 4.7%, respectively), indicating a threshold effect. DEGs were further analyzed using the knowledge-based Ingenuity Pathway Analysis (IPA) to determine altered functional and gene networks. The patterns of gene changes induced by PIA indicate sex-specific and dose-dependent effects with increased pro-inflammation in females and decreased neurodevelopment in males. These changes may underlie the documented reduced recognition memory function in male and abnormal social-cognitive behavior in female adult mice following neonatal PIA. Collectively, these results parallel clinical studies demonstrating sex-specific behavioral outcomes as a function of neonatal anemia management.

ORGANISM(S): Mus musculus

PROVIDER: GSE179877 | GEO | 2021/07/13

REPOSITORIES: GEO

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