Kaidanovich-Beilin Oksana, Milman Anat, Weizman Abraham, Pick Chaim G, Eldar-Finkelman Hagit
Departments of Human Genetics and Molecular Medicine, Felsenstein Medical Research Center, Beilinson Campus, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Biol Psychiatry. 2004 Apr 15;55(8):781-4. doi: 10.1016/j.biopsych.2004.01.008.
Inhibition of glycogen synthase kinase-3 (GSK-3) is thought to be a key feature in the therapeutic mechanism of several mood stabilizers; however, the role of GSK-3 in depressive behavior has not been determined. In these studies, we evaluated the antidepressive effect of L803-mts, a novel GSK-3 peptide inhibitor, in an animal model of depression, the mouse forced swimming test (FST).
Animals were intracerebroventricularly injected with L803-mts or with respective control peptide (cp) 1 hour, 3 hours, or 12 hours before their subjection to FST.
Animals administered L803-mts showed reduced duration of immobility at all three time points tested, as compared with cp-treated animals. Expression levels of beta-catenin, the endogenous substrate of GSK-3, increased in the hippocampus of L803-mts-treated animals by 20%-50%, as compared with cp-treated animals.
Our studies show, for the first time, that in-vivo inhibition of GSK-3 produces antidepressive-like behavior and suggest the potential of GSK-3 inhibitors as antidepressants.
糖原合酶激酶-3（GSK-3）的抑制作用被认为是几种心境稳定剂治疗机制的关键特征；然而，GSK-3在抑郁行为中的作用尚未确定。在这些研究中，我们在抑郁动物模型——小鼠强迫游泳试验（FST）中评估了新型GSK-3肽抑制剂L803-mts的抗抑郁作用。
在动物接受FST前1小时、3小时或12小时，通过脑室内注射L803-mts或相应的对照肽（cp）。
与接受cp治疗的动物相比，接受L803-mts治疗的动物在所有三个测试时间点的不动时间均缩短。与接受cp治疗的动物相比，L803-mts治疗动物海马中GSK-3的内源性底物β-连环蛋白的表达水平增加了20%-50%。
我们的研究首次表明，体内抑制GSK-3会产生抗抑郁样行为，并提示GSK-3抑制剂作为抗抑郁药的潜力。
