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Alcohol-related brain damage in humans

Quintas, Luis Eduardo M.; Erdozain, Amaia M.; Morentin, Benito; Bedford, Lynn; King, Emma; Tooth, David; Brewer, Charlotte; Wayne, Declan; Johnson, Laura; Gerdes, Henry K.; Wigmore, Peter; Callado, Luis F.; Carter, Wayne G.

Authors

Luis Eduardo M. Quintas

Amaia M. Erdozain

Benito Morentin

Lynn Bedford

Emma King

David Tooth

Charlotte Brewer

Declan Wayne

Laura Johnson

Henry K. Gerdes

Peter Wigmore

Luis F. Callado

Wayne G. Carter



Abstract

Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics.

Journal Article Type Article
Publication Date Apr 3, 2014
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 4
Article Number e93586
APA6 Citation Quintas, L. E. M., Erdozain, A. M., Morentin, B., Bedford, L., King, E., Tooth, D., …Carter, W. G. (2014). Alcohol-related brain damage in humans. PLoS ONE, 9(4), doi:10.1371/journal.pone.0093586
DOI https://doi.org/10.1371/journal.pone.0093586
Publisher URL http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093586
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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