Ahn Yong Min, Seo Myoung Suk, Kim Se Hyun, Kim Yeni, Yoon Se Chang, Juhnn Yong-Sung, Kim Yong Sik
Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Korea.
Int J Neuropsychopharmacol. 2005 Dec;8(4):607-13. doi: 10.1017/S1461145705005353. Epub 2005 May 9.
GSK-3beta is regarded as playing an important part in the pathogenesis of schizophrenia and the action of psychotomimetic agents. We observed phosphorylation of molecules associated with the GSK-3beta signalling pathway in the rat brain after MK-801 injection, which induces a schizophrenia-like state in humans. Ser9-GSK-3beta phosphorylation was increased after injection of 1 mg/kg MK-801 in the rat frontal cortex but not in the hippocampus or cerebellum. This increase peaked at 30 min and was maintained until 90 min after injection. The phosphorylation showed a dose-dependent increase up to 1 mg/kg MK-801, followed by a decrease at higher dosage. Furthermore, phosphorylation of Ser473-Akt and Ser133-CREB showed similar temporal, dose-dependent and regionally specific patterns with those of Ser9-GSK-3beta. However, phosphorylation of Dvl and Ser33-beta-catenin was not affected by MK-801. These results suggest that GSK-3beta phosphorylation by MK-801 may be associated with the Akt-GSK-3beta pathway rather than with the Wnt-Dvl-GSK3beta pathway.
糖原合成酶激酶-3β（GSK-3β）被认为在精神分裂症的发病机制和拟精神病药物的作用中发挥重要作用。我们观察了在注射MK-801后大鼠脑中与GSK-3β信号通路相关分子的磷酸化情况，MK-801可在人类中诱导出类似精神分裂症的状态。在大鼠额叶皮质注射1mg/kg MK-801后，Ser9-GSK-3β磷酸化增加，但在海马体或小脑中未增加。这种增加在注射后30分钟达到峰值，并维持到注射后90分钟。磷酸化在MK-801剂量达到1mg/kg之前呈剂量依赖性增加，在更高剂量时则下降。此外，Ser473-Akt和Ser133-CREB的磷酸化与Ser9-GSK-3β呈现出相似的时间、剂量依赖性和区域特异性模式。然而，Dvl和Ser33-β-连环蛋白的磷酸化不受MK-801影响。这些结果表明，MK-801诱导的GSK-3β磷酸化可能与Akt-GSK-3β通路有关，而不是与Wnt-Dvl-GSK3β通路有关。
