title: Cellular transfer of macromolecules across the developing choroid plexus of Monodelphis domestica.
abstract: Choroid plexus epithelial cells secrete cerebrospinal fluid (CSF) and transfer molecules from blood into CSF. Tight junctions between choroidal epithelial cells are functionally effective from early in development: the route of transfer is suggested to be transcellular. Routes of transfer for endogenous and exogenous plasma proteins and dextrans were studied in Monodelphis domestica (opossum). Pups at postnatal (P) days 1-65 and young adults were injected with biotinylated dextrans (3-70 kDa) and/or foetal protein fetuin. CSF, plasma and brain samples were collected from terminally anaesthetized animals. Choroid plexus cells containing plasma proteins were detected immunocytochemically. Numbers of plasma protein-positive epithelial cells increased to adult levels by P28, but their percentage of plexus cells declined. Numbers of cells positive for biotinylated probes increased with age, while their percentage remained constant. Colocalization studies showed specificity for individual proteins in some epithelial cells. Biotinylated probes and endogenous proteins colocalized in about 10% of cells in younger animals, increasing towards 100% by adulthood. Injections of markers into the ventricles demonstrated that protein is transferred only from blood into CSF, whereas dextrans pass in both directions. These results indicate that protein and lipid-insoluble markers are transferred by separate mechanisms present in choroid plexuses from the earliest stage of brain development, and transfer of proteins from plasma across choroid plexus epithelial cells contributes to the high protein concentration in CSF in the immature brain.
authors.affiliation: Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Shane A
authors.initials: SA
authors.lastname: Liddelow
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Dziegielewska
authors.forename: C Joakim
authors.initials: CJ
authors.lastname: Ek
authors.forename: Pia A
authors.initials: PA
authors.lastname: Johansson
authors.forename: Ann M
authors.initials: AM
authors.lastname: Potter
authors.forename: Norman R
authors.initials: NR
authors.lastname: Saunders
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000378:metabolism*; D002831:Choroid Plexus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D020547:Lateral Ventricles / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D015335:Molecular Probes / Q000032:analysis / Q000134:cerebrospinal fluid; D048309:Monodelphis / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D015335:Molecular Probes; D009419:Nerve Tissue Proteins