{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:19Z","timestamp":1791978439268,"version":"4.4.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"38","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,9,18]]},"abstract":"<jats:p>\n                    <jats:sc>d<\/jats:sc>\n                    -serine is a physiologic coagonist of NMDA receptors, but little is known about the regulation of its synthesis and synaptic turnover. The amino acid exchangers ASCT1 (Slc1a4) and ASCT2 (Slc1a5) are candidates for regulating\n                    <jats:sc>d<\/jats:sc>\n                    -serine levels. Using ASCT1 and ASCT2 KO mice, we report that ASCT1, rather than ASCT2, is a physiologic regulator of\n                    <jats:sc>d<\/jats:sc>\n                    -serine metabolism. ASCT1 is a major\n                    <jats:sc>d<\/jats:sc>\n                    -serine uptake system in astrocytes and can also export\n                    <jats:sc>l<\/jats:sc>\n                    -serine via heteroexchange, supplying neurons with the substrate for\n                    <jats:sc>d<\/jats:sc>\n                    -serine synthesis. ASCT1-KO mice display lower levels of brain\n                    <jats:sc>d<\/jats:sc>\n                    -serine along with higher levels of\n                    <jats:sc>l<\/jats:sc>\n                    -alanine,\n                    <jats:sc>l<\/jats:sc>\n                    -threonine, and glycine. Deletion of ASCT1 was associated with neurodevelopmental alterations including lower hippocampal and striatal volumes and changes in the expression of neurodevelopmental-relevant genes. Furthermore, ASCT1-KO mice exhibited deficits in motor function, spatial learning, and affective behavior, along with changes in the relative contributions of\n                    <jats:sc>d<\/jats:sc>\n                    -serine vs. glycine in mediating NMDA receptor activity. In vivo microdialysis demonstrated lower levels of extracellular\n                    <jats:sc>d<\/jats:sc>\n                    -serine in ASCT1-KO mice, confirming altered\n                    <jats:sc>d<\/jats:sc>\n                    -serine metabolism. These alterations are reminiscent of some of the neurodevelopmental phenotypes exhibited by patients with ASCT1 mutations. ASCT1-KO mice provide a useful model for potential therapeutic interventions aimed at correcting the metabolic impairments in patients with ASCT1 mutations.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1722677115","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T15:26:41Z","timestamp":1536161201000},"page":"9628-9633","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":127,"title":["ASCT1 (Slc1a4) transporter is a physiologic regulator of brain\n                    <scp>d<\/scp>\n                    -serine and neurodevelopment"],"prefix":"10.1073","volume":"115","author":[{"given":"Eitan","family":"Kaplan","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman","family":"Zubedat","sequence":"additional","affiliation":[{"name":"Department of Physiology, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Radzishevsky","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec C.","family":"Valenta","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad","family":"Rechnitz","sequence":"additional","affiliation":[{"name":"Department of Neurosciene, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Sason","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Sajrawi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Bodner","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohtarou","family":"Konno","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Hokkaido University, 060-8638 Sapporo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Esaki","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, 351-0198 Saitama, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dori","family":"Derdikman","sequence":"additional","affiliation":[{"name":"Department of Neurosciene, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, 351-0198 Saitama, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Hokkaido University, 060-8638 Sapporo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marie","family":"Billard","sequence":"additional","affiliation":[{"name":"Center of Psychiatry and Neuroscience, UMR 894, University Paris Descartes, 75014 Paris, France;"},{"name":"U1075 INSERM, Universit\u00e9 de Caen Normandie, 14032 Caen cedex 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avi","family":"Avital","sequence":"additional","affiliation":[{"name":"Department of Physiology, Rappaport Faculty of Medicine, Technion \u2013 Israel Institute of Technology, 31096 Haifa, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Wolosker","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, 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