• María José Pérez, Rocío Loyola, Francisco Canelo, Alejandra Aranguiz, Carola Tapia-Monsalves, Cesar Osorio-Fuentealba, and Rodrigo A Quintanilla.
• Laboratory of Neurodegenerative Diseases, Facultad de Ciencias de la Salud, Instituto de Investigaciones Biomedicas, Universidad Autónoma de Chile, Santiago, Chile; Centro de Investigación y Estudio del Consumo de Alcohol en Adolescentes (CIAA), Santiago, Chile.
• Neuropharmacology. 2020 Jul 1; 171: 108100.

AbstractAcute ethanol treatment induces neurodegeneration in cultured neurons and can lead to brain damage in animal models. Neuronal cells exposed to ethanol showed an increase in reactive oxygen species (ROS), oxidative damage and mitochondrial impairment contributing to synaptic failure. However, the underlying mechanisms of these events are not well understood. Here, we studied the contribution of NADPH oxidase, as a relevant source of ROS production in the brain, to mitochondrial impairment and oxidative stress induced by ethanol. We used primary hippocampal neurons subjected to an acute treatment of ethanol at increasing concentrations (25, 50, and 75 mM, 24 h), and we evaluated ROS production, mitochondrial function, and synaptic vesicle activity. Our studies showed that after ethanol administration, hippocampal neurons presented an increase in ROS levels, mitochondrial dysfunction, calcium handling defects, and synaptic impairment. Interestingly, treatment with the NADPH inhibitor, apocynin, significantly prevented oxidative stress, mitochondrial dysfunction, and the impairment of synaptic vesicle activity induced by ethanol treatment. These results indicate that NADPH oxidase could be a key participant in the molecular mechanism by which alcohol affects the brain.Copyright © 2020 Elsevier Ltd. All rights reserved.

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