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Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in
Catarina Cruz1, Manuela Meireles2, Susana M Silva1
1Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal; Center for Health Tecnology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450, Porto, Portugal.
Abstract:
Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol.
Insights
Chronic alcohol exposure partially activates microglia in the brain, leading to neuroinflammation. This partial microglial activation persists even after long-term alcohol cessation, suggesting lasting effects on the brain.
Area of Science:
- Neuroscience
- Neuroinflammation
- Alcohol-induced neuropathology
Background:
- Neuroinflammation, driven by microglial activation, is linked to various neurological disorders.
- Microglial-mediated neuroinflammation is a proposed mechanism in alcohol-induced brain damage.
Purpose of the Study:
- To investigate the impact of chronic ethanol exposure and subsequent long-term withdrawal on microglial activation and neuroinflammation.
- To analyze changes in the hippocampal formation, a brain region crucial for memory and cognition.
Main Methods:
- Male rats underwent 6 months of ethanol treatment followed by 2 months of withdrawal.
- Stereological methods and CD11b immunohistochemistry were used to quantify microglia.
- Quantitative real-time PCR (qRT-PCR) measured the expression of TNF-α, COX-2, and IL-15.
Main Results:
- Chronic alcohol consumption increased the number of activated microglia in the hippocampus, but without a full activation phenotype.
- Pro-inflammatory cytokine expression (TNF-α, COX-2) remained unchanged, while IL-15 levels were elevated.
- The observed partial microglial activation persisted even after the 2-month withdrawal period.
Conclusions:
- Chronic ethanol exposure induces a partial microglial activation state in the hippocampus without significantly increasing classical neuroinflammatory markers.
- Long-term alcohol cessation is insufficient to reverse this ethanol-induced partial microglial activation phenotype.