Markers of apoptosis induction and proliferation in the orbitofrontal cortex in alcohol dependence.
Markers of apoptosis induction and proliferation in the orbitofrontal cortex in alcohol dependence.
复制标题
酒精依赖中眶额皮质细胞凋亡诱导和增殖的标志物。
DOI：
10.1111/acer.12559
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Miguel-Hidalgo,JoseJ
中科院分区：
文献类型：
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作者：
Whittom,Angela;Villarreal,Ashley;Soni,Madhav;Owusu-Duku,Beverly;Meshram,Ashish;Rajkowska,Grazyna;Stockmeier,CraigA;Miguel-Hidalgo,JoseJ
酒精依赖（ALC）受试者在前额皮质（PFC）表现出胶质和神经元病理。然而，在许多患者中，尽管长期酗酒，神经生理障碍与灾难性细胞耗竭并不相关。目前尚不清楚，在没有重大神经系统疾病的ALC患者的PFC中，细胞退化或增殖倾向的一些相关标记物是如何改变的。方法测定29例酒精依赖者和23例非精神疾病对照者死后左眼窝额叶皮质（OFC）中促凋亡caspase 8 （C8）、X -连锁凋亡抑制蛋白（XIAP）、低pI直接IAP结合蛋白（DIABLO）、增殖细胞核抗原（PCNA）和增殖标志物Ki‐67 （Ki‐67‐IR）免疫反应细胞的水平。结果酒精受试者的14 kDa C8片段（C8‐14）水平显著升高，C8片段是C8激活的一个指标。然而，DIABLO、XIAP水平和DIABLO/XIAP比值没有变化。酗酒者的PCNA蛋白水平和Ki - 67 - IR细胞密度没有显著变化，尽管与对照组相比，老年ALC受试者的PCNA水平有所升高。结论酒精中毒患者C8激活指标显著升高，但XIAP水平、DIABLO/XIAP比值或Ki‐67标记无显著变化。这些结果将有助于解释许多ALC受试者PFC中没有灾难性的细胞损失，同时仍然与酗酒者OFC中神经胶质细胞和神经元缓慢下降的酒精相关易损性相一致。
BackgroundAlcohol‐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.MethodsLevels 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.ResultsAlcohol 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.ConclusionsSignificant 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.