title: Expression of tight junction proteins and transporters for xenobiotic metabolism at the blood-CSF barrier during development in the nonhuman primate (P. hamadryas).
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.
authors.affiliation: Institute for Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden. Electronic address: joakim.ek@neuro.gu.se.
authors.forename: C Joakim
authors.initials: CJ
authors.lastname: Ek
authors.affiliation: Institute for Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Barbara
authors.initials: B
authors.lastname: D'Angelo
authors.affiliation: Institute of Tendon and Bone Regeneration, Paracelsus Medical University, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Salzburg, Austria; Department of Traumatology and Sports Injuries, Paracelsus Medical University Salzburg, Austria; Austrian Cluster for Tissue Regeneration Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Lehner
authors.affiliation: Wyoming Pregnancy and Life Course Health Center, University of Wyoming, Laramie, WY 82071, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Nathanielsz
authors.affiliation: Department of Traumatology and Sports Injuries, Paracelsus Medical University Salzburg, Austria.
authors.forename: Cun
authors.initials: C
authors.lastname: Li
authors.affiliation: Institute for Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001711:Biotransformation; D001812:Blood-Brain Barrier / Q000254:growth & development / Q000378:metabolism*; D002831:Choroid Plexus / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D048529:Papio hamadryas / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D011247:Pregnancy; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D014018:Tissue Distribution; D015262:Xenobiotics / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D000975:Antioxidants; D026901:Membrane Transport Proteins; D062725:Tight Junction Proteins; D015262:Xenobiotics
keywords: Baboon; Blood–CSF barrier; Choroid plexus; Drug metabolism; Fetus; Neuroprotection; Primate; Xenobiotic transport