Student and Faculty Publications
Publication Date
10-17-2023
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abstract
Brain L-serine is critical for neurodevelopment and is thought to be synthesized solely from glucose. In contrast, we found that the influx of L-serine across the blood-brain barrier (BBB) is essential for brain development. We identified the endothelial Slc38a5, previously thought to be a glutamine transporter, as an L-serine transporter expressed at the BBB in early postnatal life. Young Slc38a5 knockout (KO) mice exhibit developmental alterations and a decrease in brain L-serine and D-serine, without changes in serum or liver amino acids. Slc38a5-KO brains exhibit accumulation of neurotoxic deoxysphingolipids, synaptic and mitochondrial abnormalities, and decreased neurogenesis at the dentate gyrus. Slc38a5-KO pups exhibit motor impairments that are affected by the administration of L-serine at concentrations that replenish the serine pool in the brain. Our results highlight a critical role of Slc38a5 in supplying L-serine via the BBB for proper brain development.
Keywords
Mice, Animals, Blood-Brain Barrier, Brain, Biological Transport, Ion Transport, Serine, Mice, Knockout
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Hematology Commons, Hemic and Lymphatic Diseases Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 37812701