Ahn Yong Min, Seo Myoung Suk, Kim Se Hyun, Jeon Won Je, Kim Yeni, Kang Ung Gu, Juhnn Yong-Sung, Kim Yong Sik
Department of Psychiatry and Behavioral Science and Institute of Human Behavioral Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Republic of Korea.
Psychiatry Res. 2009 May 15;167(1-2):80-7. doi: 10.1016/j.psychres.2007.12.013. Epub 2009 Apr 1.
Repeated administration of NMDA antagonists can induce behavioral alterations that mimic symptoms of psychosis, as seen in schizophrenia. JNK, one of the MAPKs, and c-Jun, its downstream target molecule, play important roles in regulating apoptosis in neural cells, and have been suggested as being associated with the pathophysiology of psychosis and the mechanism of action of some antipsychotics. We investigated changes in the JNK-c-Jun pathway and other Jun family proteins in the rat frontal cortex after single and repeated administration of MK-801 to examine acute and chronic responses. Neither the protein level nor the phosphorylation of JNK changed after single or repeated doses of MK-801. However, after repeated treatments, but not a single treatment, with MK-801, a down-regulation occurred in the protein level and of Ser73 phosphorylation of c-Jun in the rat frontal cortex. Other members of the Jun family, JunB and JunD, were unchanged. Repeated exposure to MK-801 down-regulated the phosphorylation and protein level of c-Jun in the rat frontal cortex, which may be related to the long-term effects of chronic treatment with MK-801.
反复给予N-甲基-D-天冬氨酸（NMDA）拮抗剂可诱发行为改变，这些改变类似于精神分裂症中所见的精神病症状。应激活化蛋白激酶（MAPK）之一的JNK及其下游靶分子c-Jun在调节神经细胞凋亡中起重要作用，并且有人提出它们与精神病的病理生理学及某些抗精神病药物的作用机制有关。我们研究了单次和反复给予MK-801后大鼠额叶皮质中JNK-c-Jun通路及其他Jun家族蛋白的变化，以检测急性和慢性反应。单次或反复给予MK-801后，JNK的蛋白水平和磷酸化均未改变。然而，反复给予MK-801（而非单次给予）后，大鼠额叶皮质中c-Jun的蛋白水平及其Ser73位点的磷酸化出现下调。Jun家族的其他成员JunB和JunD则未发生变化。反复接触MK-801可下调大鼠额叶皮质中c-Jun的磷酸化和蛋白水平，这可能与MK-801长期治疗的效应有关。
