Alcohol-related brain damage in humans

Quintas, Luis Eduardo M. and Erdozain, Amaia M. and Morentin, Benito and Bedford, Lynn and King, Emma and Tooth, David and Brewer, Charlotte and Wayne, Declan and Johnson, Laura and Gerdes, Henry K. and Wigmore, Peter and Callado, Luis F. and Carter, Wayne G. (2014) Alcohol-related brain damage in humans. PLoS ONE, 9 (4). e93586/1-e93586/12. ISSN 1932-6203

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1371/journal.pone.0093586
Depositing User: Eprints, Support
Date Deposited: 06 Dec 2016 15:22
Last Modified: 13 Oct 2017 16:33
URI: http://eprints.nottingham.ac.uk/id/eprint/39196

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