Gan Ping, Ding Ze-Yang, Gan Cheng, Mao Rong-Rong, Zhou Heng, Xu Lin, Zhou Qi-Xin
College of Life Sciences, Yunnan University, China; College of Basic Medicine, Kunming Medical University, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.
Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.
Psychoneuroendocrinology. 2016 Sep;71:86-93. doi: 10.1016/j.psyneuen.2016.05.011. Epub 2016 May 18.
Stressful events can generate enduring memories, which may induce certain psychiatric disorders such as post-traumatic stress disorder (PTSD). However, the underlying molecular mechanisms in these processes remain unclear. In this study, we examined whether the active form of the small G protein Rac1, Rac1-GTP, is involved in fear memory. Firstly, we detected the time course changes of Rac1-GTP after foot shocks (a strong stressor) and exogenous corticosterone (CORT) treatment. The data showed that stress and CORT induced the downregulation of Rac1-GTP in the hippocampus. Changes in the serum CORT level were negatively correlated with the level of Rac1-GTP. Additionally, a glucocorticoid receptor antagonist, RU38486, not only recovered the expression of Rac1-GTP but also impaired fear memory. Furthermore, systemic administration of NSC23766, an inhibitor of Rac1-GTP, improved fear memory at 1.5 and 24h. Therefore, Rac1 activity plays a critical role in stress-related cognition and may be a potential target in stress-related disorders.
应激事件可产生持久记忆，这可能诱发某些精神疾病，如创伤后应激障碍（PTSD）。然而，这些过程中的潜在分子机制仍不清楚。在本研究中，我们研究了小G蛋白Rac1的活性形式Rac1-GTP是否参与恐惧记忆。首先，我们检测了足部电击（一种强烈应激源）和外源性皮质酮（CORT）处理后Rac1-GTP的时间进程变化。数据显示，应激和CORT诱导海马中Rac1-GTP下调。血清CORT水平的变化与Rac1-GTP水平呈负相关。此外，糖皮质激素受体拮抗剂RU38486不仅恢复了Rac1-GTP的表达，还损害了恐惧记忆。此外，Rac1-GTP抑制剂NSC23766的全身给药在1.5小时和24小时时改善了恐惧记忆。因此，Rac1活性在应激相关认知中起关键作用，可能是应激相关疾病的潜在靶点。
