NeuroRX

, Volume 2, Issue 1, pp 27–43

Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy

Article

DOI: 10.1602/neurorx.2.1.27

Cite this article as:
Cornford, E.M. & Hyman, S. Neurotherapeutics (2005) 2: 27. doi:10.1602/neurorx.2.1.27

Summary

Immunogold electron microscopy has identified a variety of blood-brain barrier (BBB) proteins with transporter and regulatory functions. For example, isoforms of the glucose transporter, protein kinase C (PKC), and caveolin-1 are BBB specific. Isoform 1 of the facilitative glucose transporter family (GLUT1) is expressed solely in endothelial (and pericyte) domains, and ∼75% of the protein is membrane-localized in humans. Evidence is presented for a water cotransport function of BBB GLUT1. A shift in transporter polarity characterized by increased luminal membrane GLUT1 is seen when BBB glucose transport is upregulated; but a greater abluminal membrane density is seen in the human BBB when GLUT1 is downregulated. PKC colocalizes with GLUT1 within these endothelial domains during up- and downregulation, suggesting that a PKC-mediated mechanism regulates human BBB glucose transporter expression. Occludin and claudin-5 (like other tight-junctional proteins) exhibit a restricted distribution, and are expressed solely within interendothelial clefts of the BBB. GFAP (glial fibrillary acidic protein) is uniformly expressed throughout the foot-processes and the entire astrocyte. But the microvascular-facing membranes of the glial processes that contact the basal laminae are also polarized, and their transporters may also redistribute within the astrocyte. Monocarboxylic acid transporter and water channel (Aquaporin-4) expression are enriched at the glial foot-process, and both undergo physiological modulation. We suggest that as transcytosis and efflux mechanisms generate interest as potential neurotherapeutic targets, electron microscopic confirmation of their site-specific expression patterns will continue to support the CNS drug discovery process.

Key Words

Aquaporin-4 blood-brain barrier caveolin-1 claudin-5 electron microscopy GFAP GLUT1 glucose transporter occludin pegylated immunoliposome 
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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc 2005

Authors and Affiliations

  1. 1.W127 NeurologyVeterans Affairs Greater Los Angeles Healthcare SystemLos Angeles
  2. 2.Department of NeurologyUCLA School of MedicineLos Angeles
  3. 3.The Brain Research InstituteUCLA School of MedicineLos Angeles

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