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SHR Neuro Cancer Cardio Lipid Metab Microb

Parrado-Fernandez, C; Leoni, V; Saeed, A; Rodriguez-Rodriguez, P; Sandebring-Matton, A; Córdoba-Beldad, CM; Bueno, P; Gali, CC; Panzenboeck, U; Cedazo-Minguez, A; Björkhem, I.
Sex difference in flux of 27-hydroxycholesterol into the brain.
Br J Pharmacol. 2020; 72(2): Doi: 10.1111/bph.15353 [OPEN ACCESS]
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Co-authors Med Uni Graz: Gali Chaitanya Chakravarthi; Panzenboeck Ute
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Abstract:: The cerebrospinal fluid (CSF)/plasma albumin ratio (QAlb) is believed to reflect the integrity of the blood-brain barrier (BBB). Recently, we reported that QAlb is lower in females. This may be important for uptake of neurotoxic 27-hydroxycholesterol (27OH) by the brain in particular because plasma levels of 27OH are higher in males. We studied sex differences in the relation between CSF and plasma levels of 27OH and its major metabolite 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA) with QAlb. We tested the possibility of sex differences in the brain metabolism of 27OH and if its flux into the brain disrupted integrity of the BBB. We have examined our earlier studies looking for sex differences in CSF levels of oxysterols and their relation to QAlb. We utilized an in vitro model for the BBB with primary cultured brain endothelial cells to test if 27OH has a disruptive effect on this barrier. We measured mRNA and protein levels of CYP7B1 in autopsy brain samples. The correlation between CSF levels of 27OH and QAlb was higher in males whereas, with 7HOCA, the correlation was higher in females. No significant sex difference in the expression of CYP7B1 mRNA in brain autopsy samples. A correlation was found between plasma levels of 27OH and QAlb. No support was obtained for the hypothesis that plasma levels of 27OH have a disruptive effect on the BBB. The sex differences are discussed in relation to negative effects of 27OH on different brain functions. © 2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Find related publications in this database (Keywords): 27‐; hydroxycholesterol; blood–; brain barrier; neurodegeneration; sex differences