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Updated: May 18, 2026
Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
Published on: June 23, 2023
Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following
Ya-Nan Zhao1, Fang Wang1, Yan-Xia Fan1
1Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
Abstract:
Microglia function as the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes which are critical component of neurodegenerative diseases. Alcohol abuse has been considered as one of the common reasons for neurodegeneration although the causative factors are poorly understood. Here, we investigated whether activated microglia were implicated in neurodegeneration and cognitive dysfunctions in adult rats after intermittent alcohol abuse. Rats were given orally a priming dose of 5 g/kg ethanol and then 3g/kg every 8h for 4 days, followed by a 3-day ethanol-withdrawal period. These 4 days of ethanol treatments were repeated four times intermittently to simulate the binge drinking of human alcoholics. Neurodegeneration and microglial activation were detected by Fluoro-Jade B staining, Golgi staining, immunohistochemistry and ELISA, respectively, while cognitive function was assessed by Morris water maze and novel object recognition. The results showed that microglial activation and inflammatory cytokine expression were obvious in the parietal association cortex, entorhinal cortex and hippocampus accompanied by neurodegeneration following ethanol treatment. Moreover, learning and memory abilities also declined following ethanol treatments. However, the hypertrophied microglia disappeared accompanied by the decrease of inflammatory cytokines levels on day 4, and ramified microglial proliferated significantly on day 14 after ethanol withdrawal, along with a recovery from neuronal damage and cognitive impairment. Thus, the present study indicated that activated microglia might be involved in neurodegeneration and cognitive dysfunctions induced by intermittent ethanol exposure, and neurotrophic microglia appear to have a contribution to the recovery during abstinence.
Insights
Intermittent alcohol abuse activates brain microglia, causing neurodegeneration and cognitive decline. However, microglia shift to a protective role during withdrawal, aiding recovery from alcohol-induced brain damage.
Area of Science:
- Neuroscience
- Immunology
- Toxicology
Background:
- Microglia are key immune cells in the brain, crucial in neuroinflammation and neurodegenerative diseases.
- Alcohol abuse is a significant cause of neurodegeneration, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of activated microglia in neurodegeneration and cognitive dysfunction following intermittent alcohol exposure in adult rats.
Main Methods:
- Rats underwent intermittent ethanol exposure mimicking human binge drinking.
- Neurodegeneration was assessed using Fluoro-Jade B and Golgi staining.
- Microglial activation and inflammatory cytokines were measured via immunohistochemistry and ELISA.
- Cognitive function was evaluated using the Morris water maze and novel object recognition tests.
Main Results:
- Ethanol exposure led to microglial activation and increased inflammatory cytokines in specific brain regions, correlating with neurodegeneration and cognitive deficits.
- During withdrawal, hypertrophied microglia diminished, inflammatory markers decreased, and neurotrophic microglia proliferated.
- Neuronal damage and cognitive impairment showed signs of recovery during the abstinence period.
Conclusions:
- Activated microglia are implicated in alcohol-induced neurodegeneration and cognitive dysfunction.
- Neurotrophic microglia play a role in brain recovery during abstinence from alcohol.
