Alcohol-related brain damage in humans
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 tissu...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science
2014
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| Online Access: | https://eprints.nottingham.ac.uk/39196/ |
| _version_ | 1848795785516285952 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Quintas, Luis Eduardo M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:37:36Z |
| format | Article |
| id | nottingham-39196 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:37:36Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-391962020-05-04T16:47:11Z https://eprints.nottingham.ac.uk/39196/ 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. 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. Public Library of Science 2014-04-03 Article PeerReviewed 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. and Carter, Wayne G. (2014) Alcohol-related brain damage in humans. PLoS ONE, 9 (4). e93586/1-e93586/12. ISSN 1932-6203 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093586 doi:10.1371/journal.pone.0093586 doi:10.1371/journal.pone.0093586 |
| spellingShingle | 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. Alcohol-related brain damage in humans |
| title | Alcohol-related brain damage in humans |
| title_full | Alcohol-related brain damage in humans |
| title_fullStr | Alcohol-related brain damage in humans |
| title_full_unstemmed | Alcohol-related brain damage in humans |
| title_short | Alcohol-related brain damage in humans |
| title_sort | alcohol-related brain damage in humans |
| url | https://eprints.nottingham.ac.uk/39196/ https://eprints.nottingham.ac.uk/39196/ https://eprints.nottingham.ac.uk/39196/ |