ArticleProceedings of the National Academy of Sciences of the United States of America2018
ASCT1 (Slc1a4) transporter is a physiologic regulator of brain d-serine and neurodevelopment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 118 citations in OpenAlex.
- One-Carbon Metabolism and Midbrain Dopaminergic Cells in Lesch-Nyhan Disease.Molecular syndromology · 2026Review
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Uptake of L-proline by Cultured Primary Rat Astrocytes.Neurochemical research · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Nose-to-brain administration of cannabidiol-loaded polymeric micelles improves the core behavioral symptoms of autism spectrum disorder.Bioactive materials · 2026Article
- Application of Analytical Techniques to Chiral Amino Acid Profiling in Clinical Samples: Bridging Chemistry and Disease Research.Chirality · 2026Review
- Case Report of Dual Variants inClinical case reports · 2026Article
- Synphilin-1 Is Essential for Cytoskeletal Integrity of Brain Ventricular Cilia and Mitochondrial Proteostasis.International journal of molecular sciences · 2026Article
- ASCC3 promotes chemosensitivity in colorectal cancer cells.Scientific reports · 2026Article
- Serine inhibits granulosa cell ferroptosis to maintain ovarian function.Nature communications · 2026Article
- Pharmacological inhibition of PSPH reduces serine levels and epileptic seizures.Nature chemical biology · 2025Article
- Astrocyte-Neuron Metabolic Synergies in Neurological Homeostasis and Disease.Neurochemical research · 2025Review
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Mitochondrial Metabolomics in Cancer: Mass Spectrometry-Based Approaches for Metabolic Rewiring Analysis and Therapeutic Discovery.Metabolites · 2025Review
- Article
- SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- Human urine stem cells protect against cyclophosphamide-induced premature ovarian failure by inhibiting SLC1A4-mediated outflux of intracellular serine in ovarian granulosa cells.Cellular & molecular biology letters · 2025Article
- DTD1 modulates synaptic efficacy by maintaining D-serine and D-aspartate homeostasis.Science China. Life sciences · 2025Article
- Modulating the serine metabolism in human differentiated astrocytes: an integrated multi omics approach.Frontiers in cellular neuroscience · 2025Article
- Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
Abstract
d-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 d-serine levels. Using ASCT1 and ASCT2 KO mice, we report that ASCT1, rather than ASCT2, is a physiologic regulator of d-serine metabolism. ASCT1 is a major d-serine uptake system in astrocytes and can also export l-serine via heteroexchange, supplying neurons with the substrate for d-serine synthesis. ASCT1-KO mice display lower levels of brain d-serine along with higher levels of l-alanine, l-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 d-serine vs. glycine in mediating NMDA receptor activity. In vivo microdialysis demonstrated lower levels of extracellular d-serine in ASCT1-KO mice, confirming altered d-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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.