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Molecular mechanism underlying alcohol's residual effects: The role of acetaldehyde in mitochondrial dysfunction at synapses in mouse brain cortex

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dc.contributor.author Karadayian, Analía G.
dc.contributor.author Carrere, Lautaro
dc.contributor.author Czerniczyniec, Analia
dc.contributor.author Lores-Arnaiz, Silvia
dc.date.accessioned 2025-10-21T16:57:07Z
dc.date.available 2025-10-21T16:57:07Z
dc.date.issued 2025-09-17
dc.identifier.citation Karadayian AG, Carrere L, Czerniczyniec A, Lores-Arnaiz S. Molecular mechanism underlying alcohol’s residual effects: The role of acetaldehyde in mitochondrial dysfunction at synapses in mouse brain cortex. Alcohol. 17 de septiembre de 2025;129:79-91. es_ES
dc.identifier.uri https://doi.org/10.1016/j.alcohol.2025.09.004
dc.identifier.uri https://repositorio.fleni.org.ar/xmlui/handle/123456789/1419
dc.description.abstract Alcohol residual effects impose significant physiological and cognitive burdens due to acute ethanol exposure; however, its underlying mechanisms remain poorly understood. This study investigates the role of acetaldehyde, the main ethanol metabolite, in driving mitochondrial dysfunction and synaptic impairment during hangover onset. Using a mice model, we evaluated the effects of ethanol (3.8 g/kg) and the alcohol dehydrogenase inhibitor 4-methylpyrazole (4-MP) on brain cortex synaptosomes. Ethanol exposure significantly elevated serum acetaldehyde compared with control (p < 0.05), and induced mitochondrial dysfunction, as evidenced by impaired respiration (30 % decrease in basal O2 uptake vs. control), mitochondrial membrane depolarization and reduced ATP production (50 % decrease vs. control). These effects were mitigated by pre-treatment with 4-MP, which normalized acetaldehyde levels and partially restored mitochondrial function. Notably, ethanol downregulated synaptic proteins (nNOS, GluN2B, PSD-95; p < 0.05), but 4-MP failed to prevent this reduction, suggesting that acetaldehyde would not be involved in synaptic proteins alterations. Further, ethanol disrupted calcium homeostasis and nitric oxide (NO) content. Interestingly, 4-MP alone also reduced calcium uptake and NO content (p < 0.05), indicating potential off-target effects on neuronal signaling. While the reduction in acetaldehyde levels preserved mitochondrial integrity, its inability to rescue synaptic protein loss highlights the complexity of hangover pathology, involving both acetaldehyde-dependent and -independent mechanisms. Our findings underscore acetaldehyde's pivotal role in hangover-associated mitochondrial dysfunction but reveal divergent pathways in synaptic impairment. These insights advance the search for targeted hangover therapies by delineating acetaldehyde-dependent toxicity. es_ES
dc.language.iso eng es_ES
dc.publisher Elsevier es_ES
dc.subject Alcoholism es_ES
dc.subject Alcoholismo es_ES
dc.subject Mitochondrial Diseases es_ES
dc.subject Enfermedades Mitocondriales es_ES
dc.subject Acetaldehyde es_ES
dc.subject Acetaldehído es_ES
dc.subject Fomepizole es_ES
dc.subject Fomepizol es_ES
dc.title Molecular mechanism underlying alcohol's residual effects: The role of acetaldehyde in mitochondrial dysfunction at synapses in mouse brain cortex es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.description.fil Fil: Czerniczyniec, Analia. Fleni. Instituto de Neurociencias FLENI-CONICET. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.relation.ispartofVOLUME 129
dc.relation.ispartofPAGINATION 79-91
dc.relation.ispartofCOUNTRY Estados Unidos
dc.relation.ispartofCITY Nueva York
dc.relation.ispartofTITLE Alcohol
dc.relation.ispartofISSN 1873-6823
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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