Browsing by Author "Mineiro, Rafael Morais"
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- Analysis of the regulation of drug uptake and detoxification systems in the blood cerebrospinal fluid barrier: the role of sex hormones and circadian rhythmPublication . Mineiro, Rafael Morais; Paixão, Telma Alexandra Quintela; Gonçalves, Isabel Maria Theriaga Mendes VarandaThe choroid plexus (CP), localized in the brain ventricles, forms the bloodcerebrospinal fluid barrier, which, by the presence of thigh junctions, detoxification enzymes, and membrane transporters limit the traffic of molecules into the brain. Sex hormones influence several CP functions, including its activity as a circadian oscillator. This study aims to evaluate the impact of sex hormones and circadian rhythms in the function of CPs´ membrane transporters. First, we compared the diary expression of Abca1, Abcc1, Abcc4, Abcg4, and Oat3 transporters in the CP of male and female rats. We observed a circadian expression of Abcc1 and Oat3 in female rats and Abcg4 in male rats, suggesting that sex hormones influence the rhythmicity in the expression of these transporters in CP. Next, we also compared the 24 hours transcription profile of Abca1, Abcc1, Abcc4, Abcg4, and Oat3 in the CP of sham-operated and ovariectomized female rats. We found that Oat3 circadian expression is dependent on ovarian hormones. Using an in vitro model of the human blood-cerebrospinal fluid barrier, we also found that methotrexate (MTX), a very unspecific substrate in terms of transport, is transported in a circadian way across this barrier. Moreover, we demonstrate that Abcc4 is also expressed in a circadian way in the human CP epithelial papilloma cells and is partially responsible for the MTX circadian transport across the basal membrane of choroid plexus epithelial cells.