title: Markers of apoptosis induction and proliferation in the orbitofrontal cortex in alcohol dependence.
abstract: BACKGROUND
  Alcohol-dependent (ALC) subjects exhibit glial and neuronal pathology in the prefrontal cortex (PFC). 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 PFC of ALC subjects without major neurological disorders.
  
  
  METHODS
  Levels of pro-apoptotic caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive for proliferation marker Ki-67 (Ki-67-IR) were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 nonpsychiatric comparison subjects.
  
  
  RESULTS
  Alcohol subjects had significantly higher levels of the 14 kDa C8 fragment (C8-14), an indicator of C8 activation. However, there was no change in the levels of DIABLO, XIAP, or in the DIABLO/XIAP ratio. PCNA protein level and density of Ki-67-IR cells were not significantly changed in alcoholics, although PCNA levels were increased in older ALC subjects as compared to controls.
  
  
  CONCLUSIONS
  Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in XIAP level, DIABLO/XIAP ratio, or Ki-67 labeling. These results would help to explain the absence of catastrophic cell loss in the PFC of many Brigman subjects, while still being consistent with an alcoholism-related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics.
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Angela
authors.initials: A
authors.lastname: Whittom
authors.forename: Ashley
authors.initials: A
authors.lastname: Villarreal
authors.forename: Madhav
authors.initials: M
authors.lastname: Soni
authors.forename: Beverly
authors.initials: B
authors.lastname: Owusu-Duku
authors.forename: Ashish
authors.initials: A
authors.lastname: Meshram
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rajkowska
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Miguel-Hidalgo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers
keywords: Alcohol Dependence; Depression; Postmortem; Prefrontal Cortex; Vulnerability