Low GSK-3 activity in frontal cortex of schizophrenic patients
Low GSK-3 activity in frontal cortex of schizophrenic patients
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DOI：
10.1016/s0920-9964(00)00174-2
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发表时间：
2001-10-01
影响因子：
4.5
通讯作者：
Agam, G
中科院分区：
文献类型：
--
作者：
Kozlovsky, N;Belmaker, RH;Agam, G
糖原合成酶激酶-3 (GSK-3) （EC 2.7.1.37）是一种在大脑中高度丰富的蛋白激酶，参与多种细胞过程的信号转导级联反应，特别是神经发育。这种酶有两种形式，GSK-3和GSK-3。我们之前报道过精神分裂症患者死后额叶皮层GSK-3 β蛋白水平降低。为了探究GSK-3 β水平的降低是否与大脑区域有关，我们在枕叶皮层进行了研究。为了找出额叶皮层的减少是否反映在活动的改变上，我们测量了这个大脑区域的GSK-3酶活性。对15例精神分裂症、15例双相、15例单极患者和15例正常人的死后枕皮质进行GSK-3 β蛋白的Western-blot分析。通过定量测定额皮质标本中特定底物phospho-CREB的磷酸化水平来测定GSK-3活性。枕叶皮层GSK-3 β水平在四个诊断组之间没有差异。精神分裂症患者额叶皮质GSK-3活性比正常对照组低45%（分别为0.196 +/- 0.082和0.357 +/- 0.084 pmol/mg protein X min）； Kruskal-Wallis分析：卡方= 8.27,df = 3, p = 0.04。另外两个诊断组与对照组没有差异。我们的结果与精神分裂症涉及神经发育病理学的观点是一致的。(C) 2001 Elsevier Science B.V.版权所有
Glycogen synthase kinase-3 (GSK-3) (EC 2.7.1.37) is a protein kinase highly abundant in brain and involved in signal transduction cascades of multiple cellular processes, particularly neurodevelopment. Two forms of the enzyme, GSK-3 alpha and -3 beta have been previously identified. We have previously reported reduced GSK-3 beta protein levels in postmortem frontal cortex of schizophrenic patients. In an attempt to explore whether reduction of GSK-3 beta levels is brain region specific we examined it in occipital cortex. In order to find out if the reduction in frontal cortex is reflected in altered activity we measured GSK-3 enzymatic activity in this brain region. Western-blot analysis of GSK-3 beta was carried out in postmortem occipital cortex of 15 schizophrenic, 15 bipolar, and 15 unipolar patients, and 15 normal controls. GSK-3 activity was measured by quantitating the phosphorylation of the specific substrate phospho-CREB in the frontal cortex specimens. GSK-3 beta levels in occipital cortex did not differ between the four diagnostic groups. GSK-3 activity in the frontal cortex of schizophrenic patients was 45% lower than that of normal controls (0.196 +/- 0.082 and 0.357 +/- 0.084 pmol/mg protein X min, respectively; Kruskal-Wallis analysis: chi-square = 8.27, df = 3, p = 0.04). The other two diagnostic groups showed no difference from the control group. Our results are consistent with the notion that schizophrenia involves neurodevelopmental pathology. (C) 2001 Elsevier Science B.V. All rights reserved.