Micronutrient and Urate Transport in Choroid Plexus and Kidney: Implications for Drug Therapy

Abstract

With application of molecular biology techniques, there has been rapid progress in understanding how many drugs and micronutrients (e.g., vitamins) are transferred across the choroid plexus (CP), the main transport locus of the blood-cerebrospinal fluid (CSF) barrier, and the renal tubular epithelial cells. In many cases, these molecules are transported by separate, specific carriers or receptors on the apical and/or basal side of the CP or renal epithelial cells. This commentary focuses on four micronutrient transport systems in CP (ascorbic acid, folate, inositol, and riboflavin), all of which have been recently cloned, expressed and for which knockout mice models were developed and transporter localization studies performed. Also reviewed is the recently cloned uric acid transport system in human kidney in which there exists a human "knockout" model. The implications of these transport systems for drug therapy of central nervous system and renal disorders are discussed, especially with regard to methods to circumvent the blood-brain and blood-CSF barriers to deliver drugs to the brain.

Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma

“…S1a). The preferential apical localization of FRa seem to contradict currently held views of the role of FRa in taking up 5MTHF at the basolateral side of the choroid plexus 12 . However, these findings substantiate published results obtained in mouse and rat brain sections 13,14 , as well as in human tissues 15 .…”

A milk‐free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome

“…2 A low level of 5MTHF in CSF can result from decreased transport across the blood-CSF barrier. 3,4 Early diagnosis and treatment with pharmacological doses of reduced folates (5-formyltetrahydrofolate or 5-methyltetrahydrofolate) is necessary to prevent or reverse the neurological manifestations.Autoantibodies against the folate receptor (FR) were first described in mothers with a neural-tube-defect pregnancy and provided an explanation for folate deficiency in the developing embryo resulting from autoantibodies blocking folate uptake via the FR. 5 The finding of FR autoantibodies in children with CFD syndrome and the low level of 5MTHF in CSF suggested a similar mechanism by which binding of the autoantibodies to the FR on the choroid plexus would block folate transport into the CSF.…”

Antioxidant Vitamins and Their Use in Psychiatry

“…Askorbik asitin barsaklardan emilimi, böbreklerden geri emilimi, koroid pleksustaki ve beyin hücrelerindeki taşıyıcı mekanizmaların hepsi beyindeki askorbik asit miktarı üzerinde etkilidir. [50] Merkezi sinir sistemindeki askorbik asit homeostatik sistemi sayesinde beyin diğer organlara göre askorbik asit eksikliğinden daha iyi korunmaktadır. Bu sistem normal plazma konsantrasyonlarında yarı doymuş olduğu için oral veya damar yolu ile verilen yüksek askorbik asit miktarlarından da etkilenme düzeyi azalmaktadır.…”