Abstract
The choroid plexus epithelium controls the movement of solutes between the blood and the cerebrospinal 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 immunohistochemistry to identify different claudins in the choroid plexuses of developing and adult rats. Claudin-1, -2, and -3 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 selectivity, 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00418-012-1001-9) contains supplementary material, which is available to authorized users.
Highlights
A tight regulation of the neural cell microenvironment is mandatory for efficient neuronal activities
The expression of Tight junction (TJ)-associated proteins was assessed in rats at E19, postnatal day 2 (P2), postnatal day 9 (P9) and adult stages in LVCPs and 4VCPs by Quantitative real-time PCR (qRT-PCR)
While Cld-19 and Cld-22 displayed a high degree of choroidal specificity at all stages investigated, and Cld-9 followed a similar pattern of choroidal enrichment (p \ 0.05 for LVCP and 0.01 for 4VCP at E19, p \ 0.001 at P2 and in adult), Cld-6 was found enriched in choroid plexuses (CPs) as compared to cortex preparations only in the perinatal developmental stages (p \ 0.001 at E19 and 0.001 for 4VCP at P2, Fig. 1b)
Summary
A tight regulation of the neural cell microenvironment is mandatory for efficient neuronal activities. Tight junction (TJ) proteins that link the cells forming these blood–brain interfaces form the anatomical basis for this control by preventing non-specific paracellular leakage between blood and the cerebral fluids. The CPs, which are located in the different ventricles of the brain fulfill additional specific functions. They are a source of trophic factors during brain development, are responsible for controlled secretion of CSF, and are major detoxifying organs within the brain (Davson and Segal 1996; Saunders et al 2008; Strazielle and Ghersi-Egea 2000; Zappaterra and Lehtinen 2012)
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