Histochem Cell Biol (2012) 138:861–879 DOI 10.1007/s00418-012-1001-9 O R I G I N A L P A P E R Complexity and developmental changes in the expression pattern of claudins at the blood–CSF barrier Ingrid Kratzer • Alexandre Vasiljevic • Catherine Rey • Michelle Fevre-Montange • Norman Saunders • Nathalie Strazielle • Jean-Franc¸ois Ghersi-Egea Accepted: 10 July 2012 / Published online: 11 August 2012 The Author(s) 2012. This article is published with open access at Springerlink.com Abstract The choroid plexus epithelium controls the movement of solutes between the blood and the cerebro- spinal ﬂuid. It has been considered as a functionally more immature interface during brain development than in adult. The anatomical basis of this barrier is the interepithelial choroidal junction whose tightness has been attributed to the presence of claudins. We used quantitative real-time polymerase chain reaction, Western blot and immunohis- tochemistry to identify different claudins in the choroid plexuses of developing and adult rats. Claudin-1, -2, and -3 Electronic supplementary material The online version of this article (doi:10.1007/s00418-012-1001-9) contains supplementary material, which is available to authorized users. I. Kratzer A. Vasiljevic M. Fevre-Montange J.-F. Ghersi-Egea Inserm U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Lyon-1 University, 69008 Lyon, France A. Vasiljevic East Pathological Center, Lyon Public Hospitals, Lyon, France C. Rey ProﬁlXpert, UNIV-US7 INSERM-UMS 3453 CNRS Lyon, Lyon, France N. Saunders Department of Pharmacology, University of Melbourne, Melbourne, Australia N. Strazielle Brain-i, Lyon, France J.-F. Ghersi-Egea (&) Neurooncology and Neuroinﬂammation Team, INSERM U1028, CNRS UMR 5292, Lyon Neuroscience Research Center, Faculte´ de Me´decine Laennec, 7 rue G. Paradin, 69372 Lyon Cedex 08, France e-mail: jean-francois.ghersi-egea@inserm.fr were highly and selectively expressed in the choroid plexus as compared to brain or parenchyma microvessels and were localized at epithelial junctions. Claudin-6, -9, -19, and -22 also displayed a previously undescribed choroidal selec- tivity, while claudin-4, -5, and -16 were enriched in the cerebral microvessels. The choroidal pattern of tight junction protein expression in prenatal brains was already complex and included occludin and zonula occludens proteins. It differed from the adult pattern in that the pore- forming claudin-2, claudin-9, and claudin-22 increased during development, while claudin-3 and claudin-6 decreased. Claudin-2 and claudin-11 presented a mirror image of abundance between lateral ventricle and fourth ventricle choroid plexuses. Imunohistochemical analysis of human fetal and postnatal brains for claudin-1, -2, and -3 demonstrated their early presence and localization at the apico-lateral border of the choroid plexus epithelial cells. Overall, choroidal epithelial tight junctions are already complex in developing brain. The observed differences in claudin expression between developing and adult choroid plexuses may indicate developmental differences in selective blood–cerebrospinal ﬂuid transport functions. Keywords Blood–brain barrier Choroid plexus Tight junction Brain development Introduction A tight regulation of the neural cell microenvironment is mandatory for efﬁcient neuronal activities. Cerebral homeostasis largely results from the ability of both the blood–brain barrier (BBB) at the brain microvascular endothelium and the blood–cerebrospinal ﬂuid barrier (BCSFB) at the epithelium of the choroid plexuses (CPs), 123