Research for the involvement of the JNKs/c-Jun axis in the pathogenesis of stress-related psychiatric disorders

点击翻译按钮获取中文摘要

To elucidate whether the dysregulation of the c-Jun NH2-terminal kinase (JNK)/c-Jun axis contributed to the stress-induced neuronal degeneration that might be associated with the pathophysiology of stress-related psychiatric disorders, we examined the influence of various stress paradigms on the JNK/c-Jun axis in the rat brain.1)Influence of acute and repeated restraint stress on the JNK/c-Jun axis in the rat brain (frontal cortex and hippocampus)Western blot analysis revealed that acute restraint stress for 30 min, but not 15,45,90, or 120 min, significantly decreased the levels of phospho-JNK without any change in the levels of JNK1 or JNK 2 in the frontal cortex. However, the phosphorylation of ATF-2, a major substrate of JNK, was significantly decreased in response to acute restraint stress for 60 min and longer in the frontal cortex. No significant change in the phosphorylation of p38 was found in the rat brain in response to acute restraint stress.2)Influence of neonatal isolation (NI) on the JNK/c-Jun axis in the rat hippocampus with and without adulthood restraint stressBoth real-time PCR an Western blot analysis revealed that NI had no changes in the levels of JNK1 or JNK2 in adult rats. Western blot analysis revealed that NI had no changes in the levels of phospho-JNK. However, acute restraint stress in adulthood significantly decreased the hippocampal levels of JNK1, JNK2, and phospho-JNK in rats subjected to NI. In addition, the significant decrease in the phosphorylation (ser73) of c-Jun in the hippocampus was found in response to acute restraint stress in rats subjected to NI.These findings suggested that the decrease in the ATF-2 function may play a role in the stress-induced neuronal degeneration in the frontal cortex, and the decrease in the JNK/c-Jun axis function may be involved in the stress-induced neuronal degeneration in the hippocampus of adult rats subjected to early adverse experience.