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

Alicia Rodríguez-González; Marta Moya; Fernando Rodríguez de Fonseca; Raquel Gómez de Heras; Laura Orio

doi:10.3389/adar.2023.11091

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

Adv Drug Alcohol Res. 2023 Feb 24:3:11091. doi: 10.3389/adar.2023.11091. eCollection 2023.

Authors

Alicia Rodríguez-González¹, Marta Moya¹, Fernando Rodríguez de Fonseca^{1

2}, Raquel Gómez de Heras¹, Laura Orio^{1

2

3}

Affiliations

¹ Department of Psychobiology and Behavioral Sciences Methods, Faculty of Psychology, Complutense University of Madrid, Madrid, Spain.
² RIAPAd: Research Network in Primary Care in Addictions (Red de Investigación en Atención Primaria en Adicciones), Madrid, Spain.
³ Instituto de Investigación Sanitaria Hospital Universitario 12 de Octubre (imas12), Madrid, Spain.

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.

Keywords: BBB; alcohol; blood-brain-barrier; laminin; neuroinflammation; occludin; oleoylethanolamide; tight junctions.

Grants and funding

This work was supported by supported by FEDER (European Union)/Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (Spain), grant numbers: RTI2018-099535-B-I00 and PID-2021-127256OB-100 to LO. It was also supported by the Instituto de Salud Carlos III (ISCIII) and the Next-Generation EU fonds, which finances the MRR (“mecanismo para la recuperación y la resiliencia”) actions, grant number: RD21/0009/0027. AR-G was a recipient of a fellowship from Consejería de Educación, Juventud y Deporte (Comunidad de Madrid/Fondo Social Europeo).