Neuroadaptations in Human Chronic Alcoholics: Dysregulation of the NF-κB System
Author Information
Author(s): Ökvist Anna, Johansson Sofia, Kuzmin Alexander, Bazov Igor, Merino-Martinez Roxana, Ponomarev Igor, Mayfield R. Dayne, Harris R. Adron, Sheedy Donna, Garrick Therese, Harper Clive, Hurd Yasmin L., Terenius Lars, Ekström Tomas J., Bakalkin Georgy, Yakovleva Tatjana
Primary Institution: Karolinska Institute, Stockholm, Sweden
Hypothesis
Are transcription factors of the NF-κB family involved in neuroadaptations to chronic alcohol consumption in human alcoholics?
Conclusion
Chronic alcohol consumption downregulates the NF-κB system in the prefrontal cortex of human alcoholics, which may contribute to neuroplastic adaptations underlying alcoholism.
Supporting Evidence
- NF-κB DNA-binding activity was significantly lower in the prefrontal cortex of alcoholics compared to controls.
- RELA mRNA levels were decreased by 1.41 fold in alcoholics compared to controls.
- Downregulation of the p50 homodimer in alcoholics may lead to increased expression of NF-κB target genes.
- Alterations in the NF-κB system were specific to the prefrontal cortex and not observed in the motor cortex.
Takeaway
This study found that drinking a lot of alcohol changes how certain brain proteins work, which might affect how the brain learns and remembers things.
Methodology
The study analyzed DNA-binding of NF-κB proteins in postmortem brain samples from 15 chronic alcoholics and 15 control subjects using biochemical and molecular techniques.
Potential Biases
Potential bias due to the selection of postmortem samples and the exclusion of subjects with other drug abuse histories.
Limitations
The study was limited to male subjects and may not generalize to females; also, the analysis was based on postmortem brain samples.
Participant Demographics
All participants were Caucasian males, with 15 chronic alcoholics and 15 control subjects matched for age and postmortem interval.
Statistical Information
P-Value
0.003
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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