title: Developmental changes in the transcriptome of the rat choroid plexus in relation to neuroprotection.
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.
authors.affiliation: Inserm U1028, Lyon Neuroscience Research Center, Neurooncology & Neuroinflammation Team, Lyon-1 University, Lyon F-69000, France. jean-francois.ghersi-egea@inserm.fr.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kratzer
authors.forename: Shane A
authors.initials: SA
authors.lastname: Liddelow
authors.forename: Norman R
authors.initials: NR
authors.lastname: Saunders
authors.forename: Kate M
authors.initials: KM
authors.lastname: Dziegielewska
authors.forename: Nathalie
authors.initials: N
authors.lastname: Strazielle
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Ghersi-Egea
references.citation: Histochem Cell Biol. 2012 Dec;138(6):861-79
references.pmid: 22886143
references.citation: J Histochem Cytochem. 1999 Oct;47(10):1255-64
references.pmid: 10490454
references.citation: Nat Methods. 2010 Oct;7(10):843-7
references.pmid: 20835245
references.citation: J Comp Neurol. 2006 May 1;496(1):13-26
references.pmid: 16528724
references.citation: Drug Metab Dispos. 2012 Jul;40(7):1366-79
references.pmid: 22496397
references.citation: Front Pharmacol. 2012 May 18;3:89
references.pmid: 22629246
references.citation: Neuroscience. 2009 Oct 6;163(2):646-61
references.pmid: 19540314
references.citation: Mol Cell Biochem. 2011 Jun;352(1-2):143-54
references.pmid: 21359964
references.citation: Brief Bioinform. 2011 May;12(3):280-7
references.pmid: 21498551
references.citation: Carcinogenesis. 2007 Feb;28(2):465-70
references.pmid: 16920737
references.citation: Pharmacol Ther. 2012 Oct;136(1):106-30
references.pmid: 22841915
references.citation: Biochim Biophys Acta. 2003 Jan 10;1609(1):1-18
references.pmid: 12507753
references.citation: Neurosci Lett. 1986 May 15;66(2):131-4
references.pmid: 3725177
references.citation: J Biol Chem. 1999 Nov 19;274(47):33382-7
references.pmid: 10559217
references.citation: Genomics. 2007 Nov;90(5):595-609
references.pmid: 17714910
references.citation: Biochem Biophys Res Commun. 2009 Nov 20;389(3):431-6
references.pmid: 19732748
references.citation: Arch Anat Cytol Pathol. 1998;46(3):153-69
references.pmid: 9754371
references.citation: J Clin Endocrinol Metab. 2001 Jun;86(6):2734-42
references.pmid: 11397879
references.citation: Toxicol Lett. 2010 Aug 1;197(1):51-9
references.pmid: 20466047
references.citation: Cancer Res. 1998 Oct 1;58(19):4349-57
references.pmid: 9766663
references.citation: Microsc Res Tech. 2001 Jan 1;52(1):5-20
references.pmid: 11135444
references.citation: Am J Physiol Cell Physiol. 2012 May 15;302(10):C1452-9
references.pmid: 22357733
references.citation: J Biol Chem. 1988 Jan 5;263(1):480-8
references.pmid: 2891699
references.citation: J Neuropathol Exp Neurol. 2000 Jul;59(7):561-74
references.pmid: 10901227
references.citation: Eur J Neurosci. 2006 Jul;24(1):65-76
references.pmid: 16800861
references.citation: Drug Metab Rev. 2011 May;43(2):92-137
references.pmid: 21495793
references.citation: AIDS. 2003 Jul 4;17(10):1473-85
references.pmid: 12824785
references.citation: Cerebrospinal Fluid Res. 2010 Jan 11;7:2
references.pmid: 20150980
references.citation: J Neurochem. 1989 Mar;52(3):876-83
references.pmid: 2465382
references.citation: J Comp Neurol. 2008 Oct 10;510(5):497-507
references.pmid: 18680196
references.citation: Mol Pharmacol. 2002 May;61(5):982-8
references.pmid: 11961115
references.citation: J Cereb Blood Flow Metab. 2006 Sep;26(9):1165-75
references.pmid: 16395287
references.citation: PLoS One. 2012;7(3):e33554
references.pmid: 22457777
references.citation: Biochem Pharmacol. 2004 Jul 1;68(1):73-83
references.pmid: 15183119
references.citation: Mol Pharmacol. 2003 Mar;63(3):532-7
references.pmid: 12606759
references.citation: Am J Physiol Endocrinol Metab. 2013 Jan 1;304(1):E23-31
references.pmid: 23092911
references.citation: Biochim Biophys Acta. 2009 Nov;1790(11):1486-500
references.pmid: 19376195
references.citation: J Cereb Blood Flow Metab. 2011 Jan;31(1):250-61
references.pmid: 20571525
references.citation: Mol Cell Biol. 2004 Sep;24(17):7612-21
references.pmid: 15314169
references.citation: J Comp Neurol. 2003 Jun 9;460(4):451-64
references.pmid: 12717706
references.citation: J Neurochem. 2005 Sep;94(5):1420-6
references.pmid: 16111480
references.citation: Toxicol Appl Pharmacol. 2005 May 1;204(3):216-37
references.pmid: 15845415
references.citation: J Neuroinflammation. 2011 Sep 26;8:124
references.pmid: 21943033
references.citation: Biochem Pharmacol. 2009 Mar 1;77(5):897-909
references.pmid: 19041851
references.citation: J Cell Biol. 1969 Mar;40(3):648-77
references.pmid: 5765759
references.citation: J Histochem Cytochem. 2004 Apr;52(4):423-36
references.pmid: 15033994
references.citation: Drug Metab Dispos. 2003 Mar;31(3):259-65
references.pmid: 12584151
references.citation: Bioessays. 2008 Mar;30(3):237-48
references.pmid: 18293362
references.citation: J Biol Chem. 2003 Oct 31;278(44):43489-95
references.pmid: 12923172
references.citation: Physiol Res. 2012;61(Suppl 1):S89-101
references.pmid: 22827877
references.citation: J Neurosci Res. 2003 Feb 15;71(4):544-50
references.pmid: 12548710
references.citation: J Neurochem. 1994 Mar;62(3):1089-96
references.pmid: 8113796
references.citation: Mol Pharmacol. 2012 Apr;81(4):598-609
references.pmid: 22266374
references.citation: Arthritis Rheum. 2007 Oct;56(10):3326-35
references.pmid: 17907186
references.citation: J Neurosci. 1999 Aug 1;19(15):6275-89
references.pmid: 10414957
references.citation: J Neurosci Res. 1995 Jun 15;41(3):403-8
references.pmid: 7563233
references.citation: Neuropediatrics. 2008 Aug;39(4):211-8
references.pmid: 19165709
references.citation: Nature. 1976 Nov 18;264(5583):293-4
references.pmid: 1004553
references.citation: Front Pharmacol. 2012 Mar 29;3:46
references.pmid: 22479246
references.citation: J Morphol. 1966 Oct;120(2):157-87
references.pmid: 5969766
references.citation: Drug Metab Dispos. 2003 Nov;31(11):1337-45
references.pmid: 14570765
references.citation: ACS Nano. 2012 Mar 27;6(3):1925-38
references.pmid: 22303956
references.citation: Neurosci Lett. 2001 Jul 13;307(2):77-80
references.pmid: 11427304
references.citation: Neuropathol Appl Neurobiol. 1990 Aug;16(4):293-303
references.pmid: 2234311
references.citation: Am J Physiol Cell Physiol. 2007 Feb;292(2):C795-806
references.pmid: 16971491
references.citation: Brain Res. 1994 Oct 3;659(1-2):91-8
references.pmid: 7820685
references.citation: Methods Mol Biol. 2011;686:247-65
references.pmid: 21082375
references.citation: J Neurosci. 1993 May;13(5):2013-23
references.pmid: 8478688
references.citation: J Pharmacol Exp Ther. 2002 Jun;301(3):820-9
references.pmid: 12023509
references.citation: Genome Res. 2008 Sep;18(9):1509-17
references.pmid: 18550803
references.citation: J Neurochem. 1989 Sep;53(3):817-24
references.pmid: 2760621
references.citation: Neurotoxicology. 1995 Summer;16(2):349-62
references.pmid: 7566694
references.citation: Toxicol Appl Pharmacol. 1998 Sep;152(1):232-9
references.pmid: 9772218
references.citation: FASEB J. 1989 Nov;3(13):2527-31
references.pmid: 2572501
references.citation: J Biol Chem. 1994 Sep 30;269(39):24343-8
references.pmid: 7929092
references.citation: Neurosci Res. 2009 Dec;65(4):326-34
references.pmid: 19682508
references.citation: J Lipid Mediat Cell Signal. 1997 Sep;17(1):15-9
references.pmid: 9302651
references.citation: Br J Pharmacol. 2012 Mar;165(5):1260-87
references.pmid: 22013971
references.citation: Neurosci Lett. 1994 Jul 4;175(1-2):37-40
references.pmid: 7970207
references.citation: Cereb Cortex. 2010 Jun;20(6):1462-75
references.pmid: 19812240
references.citation: Eur J Endocrinol. 2004 Nov;151 Suppl 3:U25-37
references.pmid: 15554884
references.citation: Biochem Pharmacol. 2012 Nov 1;84(9):1186-95
references.pmid: 22917559
references.citation: Acta Physiol Scand. 1980 Mar;108(3):215-21
references.pmid: 6103637
references.citation: PLoS One. 2013 Jul 02;8(7):e65629
references.pmid: 23843944
references.citation: Prog Neurobiol. 1993 Feb;40(2):163-221
references.pmid: 8430212
references.citation: Brain. 2011 Nov;134(Pt 11):3236-48
references.pmid: 21964917
references.citation: J Neuropathol Exp Neurol. 2003 Dec;62(12):1254-64
references.pmid: 14692701
references.citation: Mol Pharm. 2013 May 6;10(5):1473-91
references.pmid: 23298398
references.citation: Adv Drug Deliv Rev. 2004 Oct 14;56(12):1717-40
references.pmid: 15381331
references.citation: PLoS One. 2011 Mar 24;6(3):e17820
references.pmid: 21455293
references.citation: J Biol Chem. 1998 Aug 28;273(35):22395-401
references.pmid: 9712861
references.citation: Biopharm Drug Dispos. 2013 Jan;34(1):29-44
references.pmid: 22952014
references.citation: Adv Drug Deliv Rev. 2010 Oct 30;62(13):1238-49
references.pmid: 20727377
references.citation: Adv Drug Deliv Rev. 2004 Oct 14;56(12):1741-63
references.pmid: 15381332
references.citation: J Clin Invest. 2000 Feb;105(3):279-85
references.pmid: 10675353
references.citation: Fluids Barriers CNS. 2011 Nov 04;8(1):26
references.pmid: 22053861
references.citation: J Biol Chem. 2001 Feb 16;276(7):4819-27
references.pmid: 11096091