NDLI: Novel localization of folate transport systems in the murine central nervous system

Content Provider	Springer Nature : BioMed Central
Author	Sangha, Vishal Hoque, Md. Tozammel Henderson, Jeffrey T. Bendayan, Reina
Abstract	Background Folates 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). Methods Applying 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. Results RFC, 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. Conclusions Localization 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.
Related Links	https://fluidsbarrierscns.biomedcentral.com/counter/pdf/10.1186/s12987-022-00391-3.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	20458118
DOI	10.1186/s12987-022-00391-3
Journal	Fluids and Barriers of the CNS
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2022-11-23
Access Restriction	Open
Subject Keyword	Neurosciences Hematology Neurobiology Folates Reduced folate carrier Proton-coupled folate transporter Folate receptor Blood–brain barrier Blood–cerebrospinal fluid barrier Arachnoid barrier Cerebral folate deficiency
Content Type	Text
Resource Type	Article
Subject	Neurology Developmental Neuroscience Medicine Cellular and Molecular Neuroscience
Journal Impact Factor	5.9/2023
5-Year Journal Impact Factor	7.5/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Regulation of folate transport at the mouse arachnoid barrier

Protective effects of pyrroloquinoline quinone in brain folate deficiency

Mechanisms of Membrane Transport of Folates into Cells and Across Epithelia

Active CNS delivery of oxycodone in healthy and endotoxemic pigs

Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse

Sustained choroid plexus function in human elderly and Alzheimer’s disease patients

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

Blood–brain and blood–cerebrospinal fluid barrier permeability in spontaneously hypertensive rats

Role of cationic drug-sensitive transport systems at the blood-cerebrospinal fluid barrier in para-tyramine elimination from rat brain

Novel localization of folate transport systems in the murine central nervous system

Similar Documents

Regulation of folate transport at the mouse arachnoid barrier

Protective effects of pyrroloquinoline quinone in brain folate deficiency

Mechanisms of Membrane Transport of Folates into Cells and Across Epithelia

Active CNS delivery of oxycodone in healthy and endotoxemic pigs

Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse

Sustained choroid plexus function in human elderly and Alzheimer’s disease patients

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

Blood–brain and blood–cerebrospinal fluid barrier permeability in spontaneously hypertensive rats

Role of cationic drug-sensitive transport systems at the blood-cerebrospinal fluid barrier in para-tyramine elimination from rat brain

Novel localization of folate transport systems in the murine central nervous system