4.2 Article

Sex Hormones Protect Against Amyloid-β Induced Oxidative Stress in the Choroid Plexus Cell Line Z310

Journal

JOURNAL OF NEUROENDOCRINOLOGY
Volume 28, Issue 9, Pages -

Publisher

WILEY-BLACKWELL
DOI: 10.1111/jne.12404

Keywords

choroid plexus; amyloid-beta peptide; oxidative stress; reactive oxygen species; oestrogens; androgens; transthyretin

Funding

  1. FCT [PTDC/SAU-NMC/114800/2009, SFRH/BPD/70781/2010]
  2. FEDER funds through the POCI - COMPETE - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation [007491]
  3. FCT - Foundation for Science and Technology [UID/Multi/00709]
  4. [CENTRO-07-ST24-FEDER-002015]
  5. Fundação para a Ciência e a Tecnologia [PTDC/SAU-NMC/114800/2009, SFRH/BPD/70781/2010] Funding Source: FCT

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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 beta-amyloid (A beta) 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 A beta toxicity and oxidative stress in the central nervous system. The present study aimed to understand how SHs modulate A beta-induced oxidative stress in a CP cell line (Z310 cell line) by analysing the effects of A beta(1-42) on oxidative stress, mitochondrial function and apoptosis, as well as by assessing how 17 beta-oestradiol (E-2) and 5 alpha-dihydrotestosterone (DHT) modulated these effects and the cellular uptake of A beta(1-42) by CP cells. Our findings show that E-2 and DHT treatment reduce A beta(1-42)-induced oxidative stress and the internalisation of A beta(1-42) by CP epithelial cells, highlighting the importance of considering the background of SHs and therefore sex-related differences in A beta metabolism and clearance by CP cells.

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