Differential alteration of phospholipase A2 activities in brain of patients with schizophrenia
Differential alteration of phospholipase A2 activities in brain of patients with schizophrenia
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DOI：
10.1016/s0006-8993(99)01123-3
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发表时间：
1999-03-13
期刊：
影响因子：
2.9
通讯作者：
Kish, SJ
中科院分区：
文献类型：
--
作者：
Ross, BM;Turenne, S;Kish, SJ
我们最近报道，精神分裂症患者血液中一种钙非依赖性磷脂酶A(2)的活性增加。目前的研究调查了这种障碍患者的大脑是否也发生了类似的变化，并与双相情感障碍患者进行了比较。对10例精神分裂症患者、8例双相情感障碍患者和12例正常对照尸检的颞叶、前额叶、枕叶皮质、壳核、海马体和丘脑中两类非钙刺激的磷脂酶A(2)的活性进行了测定。与对照组相比，精神分裂症患者颞叶皮质钙非依赖性磷脂酶A(2)活性增加45%，而其他脑区活性无明显变化。相比之下，钙刺激的解放军(2)活性在颞叶、前额叶皮质和壳核中降低了27%-42%，而在其他脑区没有明显变化。双相情感障碍患者脑组织磷脂酶A(2)活性正常。急性和慢性氟哌啶醇治疗的大鼠大脑皮质、小脑和纹状体中钙刺激的磷脂酶A(2)活性正常，而长期治疗的动物纹状体中钙非依赖性的磷脂酶A(2)活性降低，表明精神分裂症患者的磷脂酶A(2)活性的改变不太可能是药物的直接作用。对磷脂酶A(2)所起的细胞作用的研究表明，钙刺激的磷脂酶A(2)活性降低，就像在慢性人类可卡因使用者的纹状体中一样，可能部分是由于障碍中的多巴胺能活动增加，而钙非依赖性解放军(2)活性的增加可能与精神分裂症的脂肪酸代谢异常和氧化应激有关。(C)1999 Elsevier Science B.V.保留所有权利。
We recently reported that the activity of a calcium-independent subtype of phospholipase A(2) is increased in blood of patients with schizophrenia. The present investigation examined whether similar changes take place in brain of patients with this disorder, and for comparison, in patients with bipolar disorder. The activity of two classes of PLA(2), calcium-stimulated and independent, were assayed in autopsied temporal, prefrontal and occipital cortices, putamen, hippocampus and thalamus of 10 patients with schizophrenia, 8 patients with bipolar disorder and 12 matched control subjects. Calcium-independent PLA(2) activity was increased by 45% in the temporal cortex of patients with schizophrenia as compared with the controls but was not significantly altered in other brain areas. In contrast, calcium-stimulated PLA(2) activity was decreased by 27-42% in the temporal and prefrontal cortices and putamen, with no significant alterations in other brain regions. Brain PLA(2) activity was normal in patients with bipolar disorder. Calcium-stimulated PLA(2) activity was normal in cortex, cerebellum and striatum of rats treated acutely or chronically with haloperidol, whereas calcium-independent PLA(2) activity was decreased in striatum of chronically treated animals, indicating that altered PLA(2) activity in patients with schizophrenia is unlikely to be a direct effect of medication. Studies of the cellular role played by PLA(2) suggest that decreased calcium-stimulated PLA(2) activity, as also occurs in striatum of chronic human cocaine users, may be due, in part, to increased dopaminergic activity in the disorder, whereas increased calcium-independent PLA(2) activity may be related to abnormal fatty acid metabolism and oxidative stress in schizophrenia. (C) 1999 Elsevier Science B.V. All rights reserved.