Impairment of Serine Transport Across the Blood-Brain Barrier by Deletion of Slc38a5 Causes Developmental Delay and Motor Dysfunction

Authors

Inna Radzishevsky
Maali Odeh
Oded Bodner
Salman Zubedat
Lihi Shaulov
Maxim Litvak
Kayoko Esaki
Takeo Yoshikawa
Bella Agranovich
Wen-Hong Li
Alex Radzishevsky
Eyal Gottlieb
Avi Avital
Herman Wolosker

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

Comments

Supplementary Materials

PMID: 37812701