ReviewTransporters of the blood–brain and blood–CSF interfaces in development and in the adult☆
Section snippets
Homeostatic barriers of the brain
The barriers of the brain play critical roles in controlling the movement of various metabolites, but also drugs, between the blood and the brain – determining their concentrations and effects in the central nervous system. Fundamental to all brain barrier mechanisms is the presence of intercellular tight junctions between intimately apposed cells comprising these interfaces. Without such junctions, active and passive transfer mechanisms across the interfaces would be ineffective as diffusion
Molecular identity of transporters of the brain barriers
Each of the individual brain barriers is structurally formed by tight junctions between the cells of the interfaces (Liebner et al., 2011, Saunders et al., 2008, Wolburg et al., 2001). The critical function of these junctions is to join barrier cells together creating a physical barrier to paracellular diffusion, allowing cells to polarize with distinct luminal and abluminal components. The presence of these junctions between cells that form the interface between the periphery and the central
Barrier transporter gene expression in developing brain
Two recent papers describing transcriptome analyses that allow comparison of different stages of development of the blood–brain barrier and blood–CSF barrier have been published: Daneman et al. (2010a) of cerebral endothelial cells in postnatal and adult mouse and Liddelow et al. (2012) of fetal and adult mouse choroid plexus epithelial cells. Both used Affymetrix arrays with confirmation of some genes using qPCR. Of added importance in the work of Daneman et al. (2010a) is the comparison of
Physiological importance of transporters at barrier interfaces
Many SLC transporters regulate the movement of amino acids into the CSF and the developing brain where they are important for normal development (for review see Saunders, 1992). Most are directly involved in protein metabolism underlying cellular growth of the brain. Some are important because they act as carriers, for example, thyroid hormone transporters. The main ones so far described, Slc16a2 (MCT8) and Slco1c1 (Oatp14), have recently been identified in cerebral endothelial and choroid
A note on techniques employed in the reviewed literature
It is widely recognized that the comparison of molecular biologically-derived datasets, such as high throughput gene chip databases, is fraught with dangers and problems (Brazma et al., 2001). It is generally not recommended to compare datasets from different studies for a number of reasons. These include the type of technology used (e.g. Affymetrix genechip arrays, Illumina RNASeq, PCR, SAGE), different chemistries (e.g. Enzo versus IVT labeling kits), batch differences in chip design and
Conclusion
The mammalian brain is anatomically complex, containing diverse cell types and distinct microstructures that are surrounded and protected by a number of physical and physiological brain barriers. The large numbers of SLC transcripts present at both the blood–brain barrier and the blood–CSF barrier are likely to play crucial roles in energy metabolism, nutrient supply, as well as CSF production and neurotransmitter regulation in the brain, particularly during its development. This evidence,
Acknowledgements
N.R.S., K.M.D. and S.A.L. are members of the Neurobid Consortium, funded by the Seventh Framework Program (EU) and the National Health and Medical Research Council, Australia. SAL is funded by the American-Australian Association.
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Publication in part sponsored by the Swiss National Science Foundation through the National Center of Competence in Research (NCCR) TransCure, University of Bern, Switzerland; Director Matthias A. Hediger; Web: http://www.transcure.ch.