Atrophy and Higher Levels of Inflammatory-Related Markers in the Posterior Cerebellar Lobe Cortex in Chronic Alcohol...

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.

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.

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.

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.