RT Journal Article SR Electronic T1 NAD+-mediated rescue of prenatal forebrain angiogenesis restores postnatal behavior JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eabb9766 DO 10.1126/sciadv.abb9766 VO 6 IS 41 A1 Subburaju, Sivan A1 Kaye, Sarah A1 Choi, Yong Kee A1 Baruah, Jugajyoti A1 Datta, Debkanya A1 Ren, Jun A1 Kumar, Ashwin Srinivasan A1 Szabo, Gabor A1 Fukumura, Dai A1 Jain, Rakesh K. A1 Elkhal, Abdallah A1 Vasudevan, Anju YR 2020 UL http://advances.sciencemag.org/content/6/41/eabb9766.abstract AB Intrinsic defects within blood vessels from the earliest developmental time points can directly contribute to psychiatric disease origin. Here, we show that nicotinamide adenine dinucleotide (NAD+), administered during a critical window of prenatal development, in a mouse model with dysfunctional endothelial γ-aminobutyric acid type A (GABAA) receptors (Gabrb3 endothelial cell knockout mice), results in a synergistic repair of impaired angiogenesis and normalization of brain development, thus preventing the acquisition of abnormal behavioral symptoms. The prenatal NAD+ treatment stimulated extensive cellular and molecular changes in endothelial cells and restored blood vessel formation, GABAergic neuronal development, and forebrain morphology by recruiting an alternate pathway for cellular repair, via previously unknown transcriptional mechanisms and purinergic receptor signaling. Our findings illustrate a novel and powerful role for NAD+ in sculpting prenatal brain development that has profound implications for rescuing brain blood flow in a permanent and irreversible manner, with long-lasting consequences for mental health outcome.