Original Article

Journal of Cerebral Blood Flow & Metabolism (2006) 26, 959–973. doi:10.1038/sj.jcbfm.9600249; published online 23 November 2005

The rat blood–brain barrier transcriptome

This research was supported by a grant from the NINDS (NS37764).

Bradley E Enerson1 and Lester R Drewes1

1Department of Biochemistry and Molecular Biology and The Center for Cell and Molecular Biology, Medical School Duluth, University of Minnesota, Duluth, Minnesota, USA

Correspondence: Dr LR Drewes, Department of Biochemistry and Molecular Biology and The Center for Cell and Molecular Biology, Medical School Duluth, University of Minnesota Duluth, 1035 University Drive, Duluth, Minnesota 55812, USA. E-mail: ldrewes@d.umn.edu

Received 30 August 2005; Revised 11 October 2005; Accepted 17 October 2005; Published online 23 November 2005.

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Abstract

The blood–brain barrier (BBB) is the cellular interface between the circulating blood and neural environment, and is created by apposed endothelial cells and their intercellular tight junctions. Many aspects of how the BBB functions at the molecular level remain unresolved; therefore, we report for the first time a comprehensive gene expression profile of rat brain microvessels using serial analysis of gene expression (SAGE). We assembled a full and quantitative SAGE catalog containing 101,364 tags, of which 33% of the tags matched known genes, 51% matched expressed sequence tags (ESTs) in the Unigene database, and 16% of the tags were unassigned. The transcriptome catalog contains many new and novel transcripts among known BBB genes. A large compliment of junctional proteins and an extensive assortment of facilitated carrier and ATP-dependent transporters are included. To identify microvessel-enriched transcripts, we compared the microvessel SAGE catalog to cortex and hippocampus SAGE catalogs. This resulted in identification of 864 genes, including several known for their abundant expression at the BBB, such as the transferrin receptor (TrnR). Sorting enriched genes based on function revealed groups that encode transporters (11%), receptors (5%), proteins involved in vesicle trafficking (4%), structural proteins (10%), and components of signal transduction pathways (17%). This genomic repertoire emphasizes the unique cellular phenotype existing within the brain and further implicates the BBB as a mediator between the brain and periphery. These results may provide a useful resource and reference point from which to determine the effects of different physiological, developmental, and disease processes on BBB gene expression.

Keywords:

cerebral vascular biology, endothelial cell, expressed sequence tags, gene expression profiling, microvessels, transporters

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