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Multi-Omics Analysis Reveals Alcohol exposure affects Ferroptosis pathway in Brain

ABSTRACT: Alcohol-related brain damage (ARBD) constitutes a major global public health issue and is often comorbid with neuropsychiatric disorders such as Alzheimer's and Parkinson's diseases. Ferroptosis, a form of regulated cell death characterized by iron dependency and lipid peroxidation, has been implicated in the pathogenesis of various neurodegenerative disorders. However, the role and underlying mechanisms of ferroptosis in mediating ARBD and its associated neuropsychiatric dysfunctions remain largely unexplored. This study aimed to investigate whether chronic alcohol exposure induces neurodegenerative-like behavioral phenotypes in mice and to identify associated molecular alterations using a multi-omics approach. Behavioral assessments demonstrated that chronic alcohol exposure led to impairments in memory, exploratory activity, and motor coordination. Histopathological analysis revealed significant neuronal damage in the hippocampus and prefrontal cortex. Integrated proteomic and metabolomic profiling identified a significant enrichment of pathways related to ferroptosis and neurodegenerative diseases in alcohol-exposed mice. Additionally, biochemical assays further confirmed alcohol induced disruption of iron homeostasis, elevated reactive oxygen species, and disruption of lipid peroxidation-key features consistent with ferroptosis activation. Taken together, these findings indicate that chronic alcohol exposure induces behavioral deficits and neuronal injury in mice, and is associated with molecular and biochemical changes indicative of ferroptosis. This multi-omics evidence suggests ferroptosis as a plausible contributing pathway in alcohol-related brain damage, offering new directions for understanding its pathophysiology.

ORGANISM(S): Mus Musculus

SUBMITTER: Pei Jiang

PROVIDER: PXD075525 | iProX | Wed Mar 11 00:00:00 GMT 2026

REPOSITORIES: iProX

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Multi-Omics Analysis Reveals Alcohol exposure affects Ferroptosis pathway in Brain

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