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Expression of tight junction proteins and transporters for xenobiotic metabolism at the blood-CSF barrier during development in the nonhuman primate (P. hamadryas)

Journal article
Authors C. Joakim Ek
Barbara D'angelo
C. Lehner
P. Nathanielsz
C. Li
Carina Mallard
Published in Reproductive Toxicology
Volume 56
Pages 32-44
ISSN 0890-6238
Publication year 2015
Published at Institute of Neuroscience and Physiology
Pages 32-44
Language en
Links dx.doi.org/10.1016/j.reprotox.2015....
Keywords Choroid plexus, Fetus, Primate, Baboon, Xenobiotic transport, Neuroprotection, Drug metabolism, CEREBROSPINAL FLUID BARRIER, CHOROID-PLEXUS EPITHELIUM, MULTIDRUG-RESISTANCE, DIFFERENTIAL EXPRESSION, BRAIN INTERFACES, KNOCKOUT MICE, RNA-SEQ, RAT, MECHANISMS, PROTECTS, Reproductive Biology, Toxicology
Subject categories Clinical Medicine

Abstract

The choroid plexus (CP) is rich in barrier mechanisms including transporters and enzymes which can influence drug disposition between blood and brain. We have limited knowledge of their state in fetus. We have studied barrier mechanisms along with metabolism and transporters influencing xenobiotics, using RNAseq and protein analysis, in the CP during the second-half of gestation in a nonhuman primate (Papio hamadryas). There were no differences in the expression of the tight-junctions at the CP suggesting a well-formed fetal blood-CSF barrier during this period of gestation. Further, the fetal CP express many enzymes for phase I-III metabolisms as well as transporters suggesting that it can greatly influence drug disposition and has a significant machinery to deactivate reactive molecules with only minor gestational changes. In summary, the study suggests that from, at least, midgestation, the CP in the nonhuman primate is restrictive and express most known genes associated with barrier function and transport.

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