Markers of Apoptosis Induction and Proliferation in the Orbitofrontal Cortex in Alcohol Dependence

• Published in: Alcoholism, clinical and experimental research Vol. 38; no. 11; pp. 2790 - 2799
• Main Authors: Whittom, Angela, Villarreal, Ashley, Soni, Madhav, Owusu-Duku, Beverly, Meshram, Ashish, Rajkowska, Grazyna, Stockmeier, Craig A., Miguel-Hidalgo, Jose J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2014
• Subjects: Adult; Aged; Aged, 80 and over; Alcohol Dependence; Alcoholism - metabolism; Alcoholism - pathology; Apoptosis - physiology; Biomarkers - metabolism; Cell Proliferation - physiology; Depression; Female; Frontal Lobe - metabolism; Frontal Lobe - pathology; Humans; Male; Middle Aged; Postmortem; Prefrontal Cortex; Vulnerability; Depression; Vulnerability; Alcohol Dependence; Postmortem; Prefrontal Cortex
• ISSN: 0145-6008; 1530-0277; 1530-0277
• DOI: 10.1111/acer.12559

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 ALC subjects, while still being consistent with an alcoholism‐related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics.