ArticleFluids and barriers of the CNS2022
Novel localization of folate transport systems in the murine central nervous system.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Integrating Tumor Targeting and Half-Life Extension into a Dual-Surfaced Single-Domain ADAPT Protein.Molecular pharmaceutics · 2026Article
- Folate Receptor Alpha (FRα) and the Developing Brain: From Molecular Function to Neurodevelopmental Outcomes.Molecular neurobiology · 2026Review
- Serum and cerebral folate are normal in Down Syndrome Regression Disorder.Molecular autism · 2026Observational
- Maternal Folate Receptor Alpha Autoantibodies and Increased Fetal Nuchal Translucency as Potential Early Markers of Autism Spectrum Disorder.Brain and behavior · 2025Article
- Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches.Drug delivery and translational research · 2025Review
- Neuroprotective role of pyrroloquinoline quinone in folate deficiency-induced blood-brain barrier disruption.Fluids and barriers of the CNS · 2025Article
- Review
- Blood-CSF barrier clearance of ABC transporter substrates is suppressed by interleukin-6 in lupus choroid plexus spheroids.Fluids and barriers of the CNS · 2025Article
- The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.EMBO reports · 2025Article
- Thiamine, gastrointestinal beriberi and acetylcholine signaling.Frontiers in nutrition · 2025Review
- Accumulation of Cerebrospinal Fluid, Ventricular Enlargement, and Cerebral Folate Metabolic Errors Unify a Diverse Group of Neuropsychiatric Conditions Affecting Adult Neocortical Functions.International journal of molecular sciences · 2024Article
- Dual folate/biotin-decorated liposomes mediated delivery of methylnaphthazarin for anti-cancer activity.Scientific reports · 2024Article
- Regulation of folate transport at the mouse arachnoid barrier.Fluids and barriers of the CNS · 2024Article
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Epigenetic regulation by TET1 in gene-environmental interactions influencing susceptibility to congenital malformations.bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial One-Carbon Metabolism and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Folate Receptor Alpha-A Novel Approach to Cancer Therapy.International journal of molecular sciences · 2024Review
- Protective effects of pyrroloquinoline quinone in brain folate deficiency.Fluids and barriers of the CNS · 2023Article
- Article
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4 authors at 1 institution in 1 country.
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Abstract
backgroundFolates are a family of B9 vitamins that serve as one-carbon donors critical to biosynthetic processes required for the development and function of the central nervous system (CNS) in mammals. Folate transport is mediated by three highly specific systems: (1) folate receptor alpha (FRα; FOLR1/Folr1), (2) the reduced folate-carrier (RFC; SLC19A1/Slc19a1) and (3) the proton-coupled folate transporter (PCFT; SLC46A1/Slc46a1). Folate transport into and out of the CNS occurs at the blood-cerebrospinal fluid barrier (BCSFB), mediated by FRα and PCFT. Impairment of folate transport at the BCSFB results in cerebral folate deficiency in infants characterized by severe neurological deficiencies and seizures. In contrast to the BCSFB, CNS folate transport at other brain barriers and brain parenchymal cells has not been extensively investigated. The aim of this study is to characterize folate transport systems in the murine CNS at several known barriers encompassing the BCSFB, arachnoid barrier (AB), blood-brain barrier (BBB) and parenchymal cells (astrocytes, microglia, neurons).
methodsApplying immunohistochemistry, localization of folate transport systems (RFC, PCFT, FRα) was examined at CNS barriers and parenchymal sites in wildtype (C57BL6/N) mice. Subcellular localization of the folate transport systems was further assessed in an in vitro model of the mouse AB. Gene and protein expression was analyzed in several in vitro models of brain barriers and parenchyma by qPCR and western blot analysis.
resultsRFC, PCFT, and FRα expression was localized within the BCSFB and BBB consistent with previous reports. Only RFC and PCFT expression was detected at the AB. Varied levels of RFC and PCFT expression were detected in neuronal and glial cells.
conclusionsLocalization of RFC and PCFT within the AB, described here for the first time, suggest that AB may contribute to folate transport between the peripheral circulation and the CSF. RFC and PCFT expression observed in astrocytes and microglia is consistent with the role that one or both of these transporters may play in delivering folates into cells within brain parenchyma. These studies provide insights into mechanisms of folate transport in the CNS and may enhance our understanding of the critical role folates play in neurodevelopment and in the development of novel treatment strategies for disorders of brain folate deficiency due to impaired transporter function.
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