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.
|Proceedings of the National Academy of Sciences of the United States of America
|מזהי עצם דיגיטלי (DOIs)
|פורסם - 17 אוק׳ 2023
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