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Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection

Ingrid Kratzer1, Shane A Liddelow23, Norman R Saunders2, Kate M Dziegielewska2, Nathalie Strazielle14 and Jean-Francois Ghersi-Egea1*

Author Affiliations

1 Inserm U1028, Lyon Neuroscience Research Center, Neurooncology & Neuroinflammation Team, Lyon-1 University, Lyon F-69000, France

2 Department of Pharmacology & Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia

3 Department of Neurobiology, Stanford University, Stanford, CA 94305, USA

4 Brain-i, Lyon, France

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Fluids and Barriers of the CNS 2013, 10:25  doi:10.1186/2045-8118-10-25

Published: 1 August 2013

Abstract

Background

The choroid plexuses are the interface between the blood and the cerebrospinal fluid (CSF) contained within the ventricular spaces of the central nervous system. The tight junctions linking adjacent cells of the choroidal epithelium create a physical barrier to paracellular movement of molecules. Multispecific efflux transporters as well as drug-metabolizing and antioxidant enzymes functioning in these cells contribute to a metabolic barrier. These barrier properties reflect a neuroprotective function of the choroid plexus. The choroid plexuses develop early during embryogenesis and provide pivotal control of the internal environment throughout development when the brain is especially vulnerable to toxic insults. Perinatal injuries like hypoxia and trauma, and exposure to drugs or toxic xenobiotics can have serious consequences on neurogenesis and long-term development. The present study describes the developmental expression pattern of genes involved in the neuroprotective functions of the blood–CSF barrier.

Methods

The transcriptome of rat lateral ventricular choroid plexuses isolated from fifteen-day-old embryos, nineteen-day old fetuses, two-day old pups, and adults was analyzed by a combination of Affymetrix microarrays, Illumina RNA-Sequencing, and quantitative RT-PCR.

Results

Genes coding for proteins involved in junction formation are expressed early during development. Overall perinatal expression levels of genes involved in drug metabolism and antioxidant mechanisms are similar to, or higher than levels measured in adults. A similar developmental pattern was observed for multispecific efflux transporter genes of the Abc and Slc superfamilies. Expression of all these genes was more variable in choroid plexus from fifteen-day-old embryos. A large panel of transcription factors involved in the xenobiotic- or cell stress-mediated induction of detoxifying enzymes and transporters is also expressed throughout development.

Conclusions

This transcriptomic analysis suggests relatively well–established neuroprotective mechanisms at the blood-CSF barrier throughout development of the rat. The expression of many transcription factors early in development raises the possibility of additional protection for the vulnerable developing brain, should the fetus or newborn be exposed to drugs or other xenobiotics.

Keywords:
Cerebrospinal fluid; Development; Efflux transporter; Multidrug resistance; Detoxification; Drug metabolizing enzymes; Antioxidant