AUTHOR=Rodríguez-González Alicia , Moya Marta , Rodríguez de Fonseca Fernando , Gómez de Heras Raquel , Orio Laura TITLE=Alcohol binge drinking induces downregulation of blood-brain barrier proteins in the rat frontal cortex -but not in the hippocampus- that is not prevented by OEA pretreatment JOURNAL=Advances in Drug and Alcohol Research VOLUME=3 YEAR=2023 URL=https://www.frontierspartnerships.org/journals/advances-in-drug-and-alcohol-research/articles/10.3389/adar.2023.11091 DOI=10.3389/adar.2023.11091 ISSN=2674-0001 ABSTRACT=

Alcohol binge drinking promotes neuroinflammation which could be partially mediated by the passage of ABD-induced peripheral inflammatory molecules to the brain parenchyma through the blood-brain barrier. The BBB is sealed by tight junction proteins, which regulate the access of substances to the brain. Whether ABD alters the BBB or not remains controversial. Here, we measured the expression of BBB proteins in frontal cortex and hippocampus after an ABD procedure that was previously shown to induce neuroinflammation in the FC, and checked neuroinflammation in the hippocampus. Oleoylethanolamide is known to inhibit ABD-induced neuroinflammation in rat FC but the mechanisms of action are not clear: whereas OEA protects against alcohol-induced breakdown of the TJ proteins in the gut barrier reducing peripheral inflammation, its effect in the TJ of the BBB remains unknown. Here, we studied whether OEA (5 mg/kg, before each gavage) prevented alcohol-induced BBB dysfunction by measuring the expression of zona-occludens, occludin, and laminin in FC and hippocampus. ABD animals showed reduced laminin and occludin levels in the FC, indicative of BBB dysfunction, which is concordant with previous findings showing ABD-induced neuroinflammation in this brain region. OEA did not prevent ABD-induced changes in the BBB proteins in the FC, suggesting that the OEA main mechanism of action to inhibit neuroinflammation in this brain region is not related to prevention of TJ proteins alteration in the BBB. In the hippocampus, this ABD protocol did not alter BBB protein levels and no markers of neuroinflammation were found elevated.