Faculty, Staff and Student 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
DOI
10.1073/pnas.2302780120
PMID
37812701
PMCID
PMC10589673
PubMedCentral® Posted Date
October 2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Hematology Commons, Hemic and Lymphatic Diseases Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Material
PMID: 37812701