RT Journal Article
SR Electronic
T1 NAD<sup>+</sup>-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.