Apoptosis-related proteins and proliferation markers in the orbitofrontal cortex in major depressive disorder.
Apoptosis-related proteins and proliferation markers in the orbitofrontal cortex in major depressive disorder.
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DOI：
10.1016/j.jad.2014.02.010
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发表时间：
2014-04
影响因子：
6.6
通讯作者：
Stockmeier, Craig A.
中科院分区：
文献类型：
--
作者：
Miguel-Hidalgo, Jose J.;Whittom, Angela;Villarreal, Ashley;Soni, Madhav;Meshram, Ashish;Pickett, Jason C.;Rajkowska, Grazyna;Stockmeier, Craig A.
在重度抑郁症（MDD）中，神经活动降低，细胞对退化的弹性标记物显著减少，发生在前额叶皮层（PFC）。目前尚不清楚细胞易变性的其他相关标志物和细胞增殖标志物的变化是否与MDD相关。在MDD患者和精神正常对照组的左侧眶额皮质（OFC）尸检样本中，检测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）和增殖标记物Ki-67免疫反应阳性细胞密度（-IR）。与对照组相比，MDD受试者中C8显著增加，DIABLO与XIAP的比率较高，Ki-67-IR细胞的堆积密度较低，PCNA呈意外的年龄依赖性增加。PCNA水平显着较高的MDD患者对抗抑郁药无反应或未经抗抑郁药治疗。未使用抗抑郁药的MDD受试者的DIABLO/XIAP比值高于对照受试者。反应性评估的定性性质;抗抑郁治疗抵抗的定义仍有争议; PCNA的作用不明确。细胞易变性的标志物增加，Ki 67阳性细胞的密度为低MDD，但伴有正常XIAP水平。结果表明，抑郁症患者对细胞病理学的脆弱性增加，但不足以导致形态学上明显的细胞死亡。持续的，但低级别的细胞变性的脆弱性与减少增殖准备共存，可以解释年龄依赖性的神经元密度的减少，在抑郁症患者的眶额皮层。
In major depressive disorder (MDD), lowered neural activity and significant reductions of markers of cell resiliency to degeneration occur in the prefrontal cortex (PFC). It is still unclear whether changes in other relevant markers of cell vulnerability to degeneration and markers of cell proliferation are associated with MDD. Levels of 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 (-IR) for proliferation marker Ki-67 were measured in postmortem samples of the left orbitofrontal cortex (OFC) of subjects with MDD, and psychiatrically-normal comparison subjects. There was significant increase in C8, a higher ratio of DIABLO to XIAP, lower packing density of Ki-67-IR cells, and an unexpected age-dependent increase in PCNA in subjects with MDD vs. controls. PCNA levels were significantly higher in MDD subjects unresponsive to antidepressants or untreated with antidepressants. The DIABLO/XIAP ratio was higher in MDD subjects without antidepressants than in comparison subjects. Qualitative nature of responsiveness assessments; Definition of resistance to antidepressant treatment is still controversial; Unclear role of PCNA. Markers of cell vulnerability to degeneration are increased and density of Ki67-positive cells is low MDD, but accompanied by normal XIAP levels. The results suggest increased vulnerability to cell pathology in depression that is insufficient to cause morphologically conspicuous cell death. Persistent but low-grade vulnerability to cell degeneration coexisting with reduced proliferation readiness may explain age-dependent reductions in neuronal densities in the OFC of depressed subjects.
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