2025/03/26 by Fernando García‐Dolores, Mirielle Adelina Hernández‐Torres, Estefania Fuentes‐Medel +11
paper · doi:10.1111/nan.70011
ABSTRACT Aims Alcohol use disorder (AUD) involves excessive and chronic ethanol consumption, leading to various health issues, including cerebellar atrophy. The cerebellum is particularly susceptible to ethanol‐induced damage through neuroinflammation, oxidative stress and excitotoxicity. This damage has been documented predominantly in the anterior lobe, primarily due to its role in motor function, which is often impaired in patients with AUD. However, less is known about the impact of AUD on the posterior cerebellar lobes. In contrast, alterations in the posterior lobe have been associated with cerebellar cognitive affective syndrome (CCAS). Moreover, the cerebellum is an asymmetric structure with spatial functions being left‐lateralised. We hypothesised that the posterior cerebellar lobe in AUD cases would show increased inflammation compared with healthy controls. Methods This cross‐sectional study examined the structural integrity and neuroinflammatory state of the left posterior cerebellar lobe cortex in post‐mortem samples from nine males with chronic AUD and 9 control cases. Results Chronic AUD cases showed significant cerebellar damage. Immunohistochemistry revealed higher levels of reactive astrogliosis (GFAP), increased T reg cell markers (CD45 and FOXP3), increased mitochondria marker (MitoTracker TM ), elevated COX2 (indicating inflammation and T reg cell activity), increased cFos protein (cell activity marker), and higher caspase 3 (Casp3) levels, suggesting excessive cell death. These findings indicate that chronic AUD leads to atrophy in the left posterior cerebellar lobe cortex due to neuroinflammation driven by reactive astrogliosis, T reg cell infiltration, and COX2 activity. Conclusions The study highlights the inflammatory consequences of chronic AUD, potentially linked to cerebellar atrophy and subsequent motor and cognitive impairments. Targeting neuroinflammation could help mitigate the neurodegenerative effects of chronic AUD.