Cortical Bcl-2 protein expression and apoptotic regulation in schizophrenia
Cortical Bcl-2 protein expression and apoptotic regulation in schizophrenia
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DOI：
10.1016/s0006-3223(00)00988-4
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发表时间：
2000-10-01
影响因子：
10.6
通讯作者：
Lieberman, JA
中科院分区：
文献类型：
--
作者：
Jarskog, LF;Gilmore, JH;Lieberman, JA
背景：精神分裂症的病因仍不清楚；然而，已有人假设细胞凋亡在其中起作用。Bcl - 2是一种有效的细胞凋亡抑制剂，在中枢神经系统（CNS）中也具有神经营养活性。在几种神经退行性疾病的中枢神经系统中，Bcl - 2的表达增加。鉴于精神分裂症具有某些有限的神经退行性疾病的特征，有人假设在精神分裂症中皮质Bcl - 2的表达增加。
方法：从斯坦利基金会神经病理学联盟获取死后的颞叶皮质，样本包括匹配的对照组、精神分裂症组、双相情感障碍组和抑郁症组。通过酶联免疫吸附测定（ELISA）和蛋白质印迹法检测Bcl - 2蛋白。初步分析仅限于精神分裂症组与对照组。
结果：ELISA显示精神分裂症患者的Bcl - 2蛋白减少25%（p = 0.046），蛋白质印迹法结果也支持这一点。对精神分裂症和双相情感障碍患者的二次分析显示，接受抗精神病药物治疗的患者平均Bcl - 2水平是未使用过抗精神病药物的患者的两倍。
结论：与我们的假设相反，精神分裂症患者皮质Bcl - 2水平降低。这支持了精神分裂症不是一种典型的神经退行性疾病的观点；然而，Bcl - 2蛋白减少可能表明神经元易受促凋亡刺激和神经元萎缩的影响。此外，抗精神病药物暴露与较高的Bcl - 2水平之间的关联可能是接受维持性抗精神病治疗的患者具有良好长期预后的基础。（C）2000年生物精神病学学会。
Background: The etiology of schizophrenia remains unknown; however, a role for apoptosis has been hypothesized. Bcl-2 is a potent inhibitor of apoptosis and also exerts neurotrophic activity in the central nervous system (CNS), Bcl-2 expression is increased in the CNS of several neurodegenerarive disorders. Given that schizophrenia has certain features of a limited neurodegenerative disorder, it was hypothesized that cortical Bcl-2 expression is increased in schizophreniaMethods: Postmortem temporal cortex was obtained from the Stanley Foundation Neuropathology Consortium with matched control, schizophrenic, bipolar, and depressed subjects, Bcl-2 protein was measured by enzyme-linked immunoassay (ELISA) and Western blot. Primary analysis was limited to schizophrenia versus control subjects,Results: The ELISA demonstrated 25% less Bcl-2 protein in schizophrenia (p = .046), supported by Western blot results. A secondary analysis of schizophrenic and bipolar subjects revealed twofold higher mean Bcl-2 in antipsychotic-treated versus neuroleptic-naive subjects.Conclusions: Contrary to our hypothesis, cortical Bcl-2 was reduced in schizophrenia. This supports the notion that schizophrenia is not a classic neurodegenerative disorder; however, less Bcl-2 protein may signal neuronal vulnerability to proapoptotic stimuli and to neuronal atrophy. Also, the association between neuroleptic exposure and higher Bcl-2 levels could underlie the favorable long-term outcomes of patients who receive maintenance antipsychotic treatment. (C) 2000 Society of Biological Psychiatry.