The harmful use of alcohol is one of the leading risk factors for population health worldwide. Subjects with alcohol use disorder may be affected by the consequences of recurrent alcohol abuse on the body, including alcohol-related liver disease and alcohol-related brain injury. Our laboratory recently investigated morphological and molecular alterations of rat brain microvascular endothelial cells (RBE4), an in vitro monolayer model of the blood-brain barrier (BBB), following alcohol exposure. To assess whether alcohol caused a concentration-related response, cells were treated with 35, 50, 75, or 100 mM ethyl alcohol at different times. These concentrations are equal or equivalent to two or three times the legal limits for blood alcohol concentration in Italy. Some of the mechanisms involved in alcohol-induced pathologies including cellular changes, apoptosis and reactive oxygen species (ROS) generation were evaluated. Our findings demonstrate that alcohol metabolism in RBE4 cells induces oxidative and endoplasmic reticulum (ER) stress by ROS production and GRP78 chaperone up-regulation respectively. Moreover, the morphological determinations performed on the RBE4 monolayer following alcohol exposure evidence a gradual transition from “dot-like” to “zipper-like” structures of ZO-1 staining as well as small gap formation indicating cytoskeleton rearrangements. Better understanding of these processes will reveal additional potential target for therapy in brain injuries caused by alcohol abuse or in several CNS diseases involving BBB impairment.

BLOOD-BRAIN BARRIER DYSFUNCTION FOLLOWING ALCOHOL EXPOSURE / Donatello Carrino, Jacopo Junio Valerio Branca, Gabriele Morucci, Ferdinando Paternostro, Massimo Gulisano, Alessandra Pacini. - In: EUROPEAN JOURNAL OF HISTOCHEMISTRY. - ISSN 2038-8306. - ELETTRONICO. - 64:(2020), pp. 4-4. (Intervento presentato al convegno 29th National Conference of the Italian Group for the Study of Neuromorphology “Gruppo Italiano per lo Studio della Neuromorfologia” G.I.S.N. tenutosi a Bari nel 15-16 November) [10.4081/ejh.2020.3121].

BLOOD-BRAIN BARRIER DYSFUNCTION FOLLOWING ALCOHOL EXPOSURE

Donatello Carrino
;
Jacopo Junio Valerio Branca;Gabriele Morucci;Ferdinando Paternostro;Massimo Gulisano;Alessandra Pacini
2020

Abstract

The harmful use of alcohol is one of the leading risk factors for population health worldwide. Subjects with alcohol use disorder may be affected by the consequences of recurrent alcohol abuse on the body, including alcohol-related liver disease and alcohol-related brain injury. Our laboratory recently investigated morphological and molecular alterations of rat brain microvascular endothelial cells (RBE4), an in vitro monolayer model of the blood-brain barrier (BBB), following alcohol exposure. To assess whether alcohol caused a concentration-related response, cells were treated with 35, 50, 75, or 100 mM ethyl alcohol at different times. These concentrations are equal or equivalent to two or three times the legal limits for blood alcohol concentration in Italy. Some of the mechanisms involved in alcohol-induced pathologies including cellular changes, apoptosis and reactive oxygen species (ROS) generation were evaluated. Our findings demonstrate that alcohol metabolism in RBE4 cells induces oxidative and endoplasmic reticulum (ER) stress by ROS production and GRP78 chaperone up-regulation respectively. Moreover, the morphological determinations performed on the RBE4 monolayer following alcohol exposure evidence a gradual transition from “dot-like” to “zipper-like” structures of ZO-1 staining as well as small gap formation indicating cytoskeleton rearrangements. Better understanding of these processes will reveal additional potential target for therapy in brain injuries caused by alcohol abuse or in several CNS diseases involving BBB impairment.
2020
Proceedings of the 29th National Conference of the Italian Group for the Study of Neuromorphology “Gruppo Italiano per lo Studio della Neuromorfologia” G.I.S.N
29th National Conference of the Italian Group for the Study of Neuromorphology “Gruppo Italiano per lo Studio della Neuromorfologia” G.I.S.N.
Bari
15-16 November
Donatello Carrino, Jacopo Junio Valerio Branca, Gabriele Morucci, Ferdinando Paternostro, Massimo Gulisano, Alessandra Pacini
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1220211
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