Daño cerebral relacionado al alcohol en humanos
Una investigación conjunta de la Universidad del País Vasco y de la Universidad de Nottingham ha identificado, por primera vez, los daños estructurales a escala molecular ocasionados en el cerebro por el consumo crónico excesivo de alcohol. En concreto, los autores han determinado las alteraciones que se producen en las neuronas de la zona prefrontal del cerebro, la zona evolutivamente más avanzada y que controla las funciones ejecutivas como la planificación y el diseño de estrategias, la memoria de trabajo, la atención selectiva o el control de la conducta. Los autores analizaron post mortem el cerebro de 20 personas diagnosticadas de abuso o dependencia del alcohol y otras 20 personas sin problemas de alcoholismo. En el estudio de la corteza prefrontal, los investigadores detectaron alteraciones del citoesqueleto neuronal en los cerebros de pacientes alcohólicos; en concreto, en las proteínas α-tubulina, β- tubulina y espectrina βII. Las tubulinas conforman el citoesqueleto de las neuronas, su arquitectura, y las espectrinas tienen como función el mantenimiento de la forma celular. Por tanto, los cambios de la estructura neuronal inducidos por el etanol podrían afectar a la organización, capacidad de relación y funcionamiento de la red neuronal, y podrían explicar gran parte de las alteraciones de comportamiento, cognitivas y de aprendizaje atribuidas a las personas que sufren alcoholismo.
Alcohol-related brain damage in humans.
Erdozain AM, Morentin B, Bedford L, King E, Tooth D, Brewer C, Wayne D, Johnson L, Gerdes HK, Wigmore P, Callado LF, Carter WG.
PLoS One. 2014 Apr 3;9(4):e93586. doi: 10.1371/journal.pone.0093586. eCollection 2014.
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 isoaspartatedamage 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 ofbrain 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.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974765/
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0093586&representation=PDF
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
Una investigación conjunta de la Universidad del País Vasco y de la Universidad de Nottingham ha identificado, por primera vez, los daños estructurales a escala molecular ocasionados en el cerebro por el consumo crónico excesivo de alcohol. En concreto, los autores han determinado las alteraciones que se producen en las neuronas de la zona prefrontal del cerebro, la zona evolutivamente más avanzada y que controla las funciones ejecutivas como la planificación y el diseño de estrategias, la memoria de trabajo, la atención selectiva o el control de la conducta. Los autores analizaron post mortem el cerebro de 20 personas diagnosticadas de abuso o dependencia del alcohol y otras 20 personas sin problemas de alcoholismo. En el estudio de la corteza prefrontal, los investigadores detectaron alteraciones del citoesqueleto neuronal en los cerebros de pacientes alcohólicos; en concreto, en las proteínas α-tubulina, β- tubulina y espectrina βII. Las tubulinas conforman el citoesqueleto de las neuronas, su arquitectura, y las espectrinas tienen como función el mantenimiento de la forma celular. Por tanto, los cambios de la estructura neuronal inducidos por el etanol podrían afectar a la organización, capacidad de relación y funcionamiento de la red neuronal, y podrían explicar gran parte de las alteraciones de comportamiento, cognitivas y de aprendizaje atribuidas a las personas que sufren alcoholismo.
Alcohol-related brain damage in humans.
Erdozain AM, Morentin B, Bedford L, King E, Tooth D, Brewer C, Wayne D, Johnson L, Gerdes HK, Wigmore P, Callado LF, Carter WG.
PLoS One. 2014 Apr 3;9(4):e93586. doi: 10.1371/journal.pone.0093586. eCollection 2014.
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 isoaspartatedamage 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 ofbrain 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.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974765/
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0093586&representation=PDF
Atentamente
Anestesiología y Medicina del Dolor
www.anestesia-dolor.org
