Details

Autor(en) / Beteiligte

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

Titel

Impairment of serine transport across the blood-brain barrier by deletion of Slc38a5 causes developmental delay and motor dysfunction

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2023-10, Vol.120 (42), p.e2302780120-e2302780120

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.