Whole brain RNA-seq from mice under in utero and adult caloric restriction
Prenatal caloric restriction (CR) can program long-lasting changes in brain endothelial function, potentially influencing neurovascular health and contributing to neurodevelopmental disorders. In this study, we investigated the effects of maternal CR on brain endothelial transcriptional states and blood-brain barrier (BBB) integrity in a mouse model. Using RNA sequencing and deconvolution methods, we identified significant alterations in endothelial tip and stalk cell proportions, with a marked increase in endothelial tip cells in offspring subjected to prenatal CR. These changes were associated with disrupted vascular stability, as indicated by shifts in gene expression related to angiogenesis and BBB function. Notably, the transcriptional reprogramming observed in prenatal CR conditions suggests a predisposition to altered neurovascular function in adulthood, which could have implications for psychiatric disorders (such as schizophrenia ). Our findings support the hypothesis that early-life nutritional stress can have enduring effects on neurovascular integrity and may predispose individuals to neurodevelopmental diseases, highlighting the need for further investigation into the mechanisms linking prenatal nutrition and psychiatric outcomes.