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.

Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause

“…It has been proposed that brain differences in the cholinergic system among males and females may underlie the differences in response to acetylcholinesterase inhibitors (AChEI) and the rate of progression of AD between sexes, with a higher benefit of AChEI treatment delaying the progression of the disease in men than women ( Giacobini and Pepeu, 2018 ). Estrogenic compounds are neuroprotective against Aβ toxicity in vitro ( Svensson and Nordberg, 1999 ; Szego et al, 2011 ; Xing et al, 2011 ; Bagheri et al, 2012 ; Wu et al, 2012 ; Napolitano et al, 2014 ; Costa et al, 2016 ; Li et al, 2017 ; You et al, 2017 ; Yang et al, 2019 ) as well as in vivo models of AD ( Bagheri et al, 2011 ; Limon et al, 2012 ; Pompili et al, 2012 ; Zhao et al, 2013 ). In one of these preclinical studies, to investigate the effect of estrogen on the cholinergic deficit in AD, different Aβ assemblies were injected in the nucleus basalis magnocellular (NBM) of sham control and OVX mice, and the viability of cholinergic cells was measured ( Szego et al, 2011 ).…”

Hepatoprotective Effects of Sweet Cherry Extracts (cv. Saco)

“…After 24 h, different concentrations of cherry fractions dissolved in medium containing 0.5% (v/v) dimethylsulfoxide (DMSO) (6.25-100 µg/mL) were added. To assess the cytotoxicity effects after exposure to the fractions, plates were incubated for 24, 48 and 72 h [28][29][30][31][32]. On the other hand, for evaluating the antioxidant potential, preliminary assays were performed to choose the appropriate concentration and exposure time of each oxidative stress inductor able to cause around 50% cell death (data not shown).…”

Amyloid precursor protein, an androgen‐regulated gene, is targeted by RNA‐binding protein PSF/SFPQ in neuronal cells

“…Aβ accumulation induces mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative damage to the choroid plexus epithelium, which eventually compromises on the Aβ clearance (Leuner, Müller, & Reichert, ). DHT prevents ROS production in the choroid plexus epithelium and elevates the expression of Aβ scavenger transthyretin in an AR‐dependent manner (Costa et al, ; Vasconsuelo, Milanesi, & Boland, ; Yan et al, ). These findings demonstrate that androgen hormones significantly prevent Aβ deposition in the brain.…”