Abstract
The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases.
Highlights
The composition of the interstitial fluid (ISF) of the central nervous system (CNS) is tightly controlled by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) in order to ensure the appropriate microenvironments for neuronal signaling [1,2]
This review focuses on the recent knowledge advances on the transporter proteins expressed in choroid plexus (CP) epithelial cells—in particular, those belonging to the facilitated diffusion glucose transporter (SLC2A/GLUT) and sodium/glucose cotransporter (SLC5A/SGLT) families, which are specific to hexose and urate transport
The transporters and ion channels expressed in CP epithelial cells that are involved in the secretion of CSF have been extensively studied [5,10,13,23]
Summary
The composition of the interstitial fluid (ISF) of the central nervous system (CNS) is tightly controlled by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) in order to ensure the appropriate microenvironments for neuronal signaling [1,2]. The electrical resistance of the CP epithelial cell layer is in the intermediate range (~150 Ω·cm2), indicating its permeable nature similar to some kidney and gut segments [1,4,8,9] These two structures function as the interface between blood and brain fluid (i.e., brain ISF and CSF), preventing plasma proteins such as albumin and circulating blood cells (erythrocytes and leukocytes) from entering freely into the brain parenchyma. In addition to their barrier function, the BBB and BCSFB are responsible for maintaining the brain microenvironment by regulating the supply of essential nutrients such as glucose and amino acids, the exchange of electrolytes between the brain ISF and the circulating blood, and the removal of metabolic wastes and neurotoxic substances such as drug metabolites and amyloid β (Aβ) [1,2,3,11,12] To fulfill such needs, brain capillary endothelial cells and CP epithelial cells are equipped with several specific transporter proteins [1,2,3]. It describes the similarity of CP epithelial cells to renal proximal tubular epithelial cells, in terms of their morphological properties and the expression repertoire of transporter proteins
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