Ross B M, Turenne S, Moszczynska A, Warsh J J, Kish S J
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada.
Brain Res. 1999 Mar 13;821(2):407-13. doi: 10.1016/s0006-8993(99)01123-3.
We recently reported that the activity of a calcium-independent subtype of phospholipase A2 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 PLA2, 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 PLA2 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 PLA2 activity was decreased by 27-42% in the temporal and prefrontal cortices and putamen, with no significant alterations in other brain regions. Brain PLA2 activity was normal in patients with bipolar disorder. Calcium-stimulated PLA2 activity was normal in cortex, cerebellum and striatum of rats treated acutely or chronically with haloperidol, whereas calcium-independent PLA2 activity was decreased in striatum of chronically treated animals, indicating that altered PLA2 activity in patients with schizophrenia is unlikely to be a direct effect of medication. Studies of the cellular role played by PLA2 suggest that decreased calcium-stimulated PLA2 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 PLA2 activity may be related to abnormal fatty acid metabolism and oxidative stress in schizophrenia.
我们最近报道，精神分裂症患者血液中一种不依赖钙的磷脂酶A2亚型的活性增加。本研究调查了患有这种疾病的患者大脑中是否发生了类似的变化，并与双相情感障碍患者进行了比较。在10名精神分裂症患者、8名双相情感障碍患者和12名匹配的对照受试者的尸检颞叶、前额叶和枕叶皮质、壳核、海马体和丘脑中，检测了两类磷脂酶A2（钙刺激型和非钙依赖型）的活性。与对照组相比，精神分裂症患者颞叶皮质中不依赖钙的磷脂酶A2活性增加了45%，但在其他脑区没有显著变化。相比之下，颞叶和前额叶皮质以及壳核中钙刺激型磷脂酶A2活性降低了27%-42%，其他脑区没有显著变化。双相情感障碍患者的脑磷脂酶A2活性正常。急性或慢性给予氟哌啶醇治疗的大鼠，其皮质、小脑和纹状体中钙刺激型磷脂酶A2活性正常，而慢性治疗动物的纹状体中不依赖钙的磷脂酶A2活性降低，这表明精神分裂症患者磷脂酶A2活性的改变不太可能是药物的直接作用。对磷脂酶A2所起细胞作用的研究表明，钙刺激型磷脂酶A2活性降低，这在慢性使用可卡因的人类纹状体中也会出现，可能部分是由于该疾病中多巴胺能活性增加，而不依赖钙的磷脂酶A2活性增加可能与精神分裂症中异常的脂肪酸代谢和氧化应激有关。
