{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:28:59Z","timestamp":1789241339455,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T00:00:00Z","timestamp":1416787200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["MH82297"],"award-info":[{"award-number":["MH82297"]}]},{"name":"NIH","award":["P30 GM103328"],"award-info":[{"award-number":["P30 GM103328"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alcohol\u2010dependent (<jats:styled-content style=\"fixed-case\">ALC<\/jats:styled-content>) subjects exhibit glial and neuronal pathology in the prefrontal cortex (<jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content>). However, in many patients, neurophysiological disturbances are not associated with catastrophic cell depletion despite prolonged alcohol abuse. It is still unclear how some relevant markers of a cell's propensity to degenerate or proliferate are changed in the <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">ALC<\/jats:styled-content> subjects without major neurological disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Levels of pro\u2010apoptotic caspase 8 (C8), X\u2010linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low <jats:styled-content style=\"fixed-case\">pI<\/jats:styled-content> (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive for proliferation marker Ki\u201067 (Ki\u201067\u2010IR) were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 nonpsychiatric comparison subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol subjects had significantly higher levels of the 14\u00a0kDa C8 fragment (C8\u201014), an indicator of C8 activation. However, there was no change in the levels of <jats:styled-content style=\"fixed-case\">DIABLO<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> XIAP<\/jats:styled-content>, or in the <jats:styled-content style=\"fixed-case\">DIABLO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">XIAP<\/jats:styled-content> ratio. <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> protein level and density of Ki\u201067\u2010<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> cells were not significantly changed in alcoholics, although <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> levels were increased in older <jats:styled-content style=\"fixed-case\">ALC<\/jats:styled-content> subjects as compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in <jats:styled-content style=\"fixed-case\">XIAP<\/jats:styled-content> level, <jats:styled-content style=\"fixed-case\">DIABLO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">XIAP<\/jats:styled-content> ratio, or Ki\u201067 labeling. These results would help to explain the absence of catastrophic cell loss in the <jats:styled-content style=\"fixed-case\">PFC<\/jats:styled-content> of many <jats:styled-content style=\"fixed-case\">ALC<\/jats:styled-content> subjects, while still being consistent with an alcoholism\u2010related vulnerability to slow decline in glial cells and neurons in the <jats:styled-content style=\"fixed-case\">OFC<\/jats:styled-content> of alcoholics.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12559","type":"journal-article","created":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T15:41:43Z","timestamp":1416843703000},"page":"2790-2799","source":"Crossref","is-referenced-by-count":9,"title":["Markers of Apoptosis Induction and Proliferation in the Orbitofrontal Cortex in Alcohol Dependence"],"prefix":"10.1111","volume":"38","author":[{"given":"Angela","family":"Whittom","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Human Behavior University of Mississippi Medical 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