The Psychiatric Institute, University of Illinois at Chicago, Department of Psychiatry, Chicago, IL 60612, USA.
J Psychiatr Res. 2010 Feb;44(3):143-8. doi: 10.1016/j.jpsychires.2009.07.009. Epub 2009 Aug 29.
Glycogen synthase kinase (GSK)-3beta, an important component of the Wnt signaling pathway, is involved in numerous cellular functions. That GSK-3beta may be involved in the pathophysiology of bipolar (BP) illness is based on the observation that lithium, a mood-stabilizing drug, inhibits GSK-3beta both in vitro and in vivo. We determined the protein expression of GSK-3beta in the cytosol and membrane fractions of the platelets obtained from patients with major depressive disorder (MDD) and BP illness, before treatment and after treatment with antidepressants or mood-stabilizing drugs, respectively. Protein expression was determined using the Western blot technique. We observed that the protein expression of GSK-3beta was significantly reduced in the membrane and cytosol fractions of platelets from drug-free patients with BP illness, but not from the drug-free patients with MDD, compared with normal control subjects. Treatment with mood-stabilizing drugs significantly increased the protein expression of GSK-3beta in the membrane and cytosol fractions of platelets from BP patients compared with pre-treatment levels, and the post-treatment levels were similar to those observed in normal control subjects. On the other hand, there was no significant effect of treatment with antidepressants on GSK-3beta protein expression either in the membrane or in the cytosol fractions of platelets from MDD patients. These results suggest that GSK-3beta may play an important role in the pathophysiology of BP illness but not MDD and that its abnormality may be corrected by treatment with mood-stabilizing drugs, suggesting that GSK-3beta may be a state rather than a trait marker for BP illness.
糖原合酶激酶（GSK）-3β是 Wnt 信号通路的重要组成部分，参与许多细胞功能。GSK-3β 可能参与双相情感障碍（BP）疾病的病理生理学，这是基于观察到锂，一种情绪稳定药物，在体外和体内均抑制 GSK-3β。我们分别在抗抑郁药或情绪稳定剂治疗前后，测定了来自未用药的 BP 患者和 MDD 患者的血小板的胞质和膜部分中 GSK-3β 的蛋白表达。使用 Western blot 技术确定蛋白表达。我们观察到，与正常对照组相比，未用药的 BP 患者的血小板的膜和胞质部分中 GSK-3β 的蛋白表达显著降低，但未用药的 MDD 患者的则没有。与治疗前相比，情绪稳定剂治疗后显著增加了 BP 患者血小板的膜和胞质部分中 GSK-3β 的蛋白表达，且治疗后的水平与正常对照组相似。另一方面，抗抑郁药治疗对 MDD 患者血小板的膜和胞质部分中 GSK-3β 的蛋白表达均无显著影响。这些结果表明，GSK-3β 可能在 BP 疾病的病理生理学中起重要作用，但在 MDD 中则没有，其异常可能通过情绪稳定剂治疗得到纠正，这表明 GSK-3β 可能是 BP 疾病的状态而非特征标志物。
