title: Sex Hormones Protect Against Amyloid-β Induced Oxidative Stress in the Choroid Plexus Cell Line Z310.
abstract: The choroid plexus (CP) epithelium is a unique structure in the brain that forms an interface between the peripheral blood on the basal side and the cerebrospinal fluid (CSF) on the apical side. It is a relevant source of many polypeptides secreted to the CSF with neuroprotective functions and also participates in the elimination and detoxification of brain metabolites, such as β-amyloid (Aβ) removal from the CSF through transporter-mediated influx. The CP is also a target tissue for sex hormones (SHs) that have recognised neuroprotective effects against a variety of insults, including Aβ toxicity and oxidative stress in the central nervous system. The present study aimed to understand how SHs modulate Aβ-induced oxidative stress in a CP cell line (Z310 cell line) by analysing the effects of Aβ1-42 on oxidative stress, mitochondrial function and apoptosis, as well as by assessing how 17β-oestradiol (E2 ) and 5α-dihydrotestosterone (DHT) modulated these effects and the cellular uptake of Aβ1-42 by CP cells. Our findings show that E2 and DHT treatment reduce Aβ1-42 -induced oxidative stress and the internalisation of Aβ1-42 by CP epithelial cells, highlighting the importance of considering the background of SHs and therefore sex-related differences in Aβ metabolism and clearance by CP cells.
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Costa
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: H
authors.identifier: 0000-0002-6218-6192
authors.initials: H
authors.lastname: Marcelino
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Gonçalves
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: T
authors.initials: T
authors.lastname: Quintela
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Tomás
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: A C
authors.initials: AC
authors.lastname: Duarte
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: A M
authors.initials: AM
authors.lastname: Fonseca
authors.affiliation: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: C R A
authors.identifier: 0000-0001-6074-7825
authors.initials: CR
authors.lastname: Santos
mesh_terms: D043582:5-alpha-Dihydroprogesterone / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D018696:Neuroprotective Agents; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D011228:Prealbumin / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D012739:Gonadal Steroid Hormones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011228:Prealbumin; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; C075222:amyloid beta-protein (1-42); D004958:Estradiol; D043582:5-alpha-Dihydroprogesterone; D003576:Electron Transport Complex IV
keywords: amyloid-β peptide; androgens; choroid plexus; oestrogens; oxidative stress; reactive oxygen species; transthyretin