中科院心理所林文娟和亓晓丽等专家为进一步研究ERK-CREB信号系统在抑郁行为中的可能作用，他们探讨了抗抑郁药氟西汀(fluoxetine)对大鼠脑ERK-CREB信号系统及抑郁样行为的作用。他们前期的研究工作提示，细胞外信号调节激酶(ERK)和cAMP反应元件结合蛋白(CREB)信号系统可能与抑郁行为的分子机制有关。
氟西汀是一种临床广泛应用的抗抑郁药物，通过抑制中枢神经系统突触间‘隙5-羟色胺’的再摄取发挥临床疗效。该研究将实验大鼠分为对照组、氟西汀组、应激组和应激后氟西汀干预组。研究结果表明，21天的强迫游泳应激显著降低了应激组大鼠在海马和前额叶皮质ERK-CREB信号系统的活性水平，主要体现为应激大鼠海马和前额叶皮质P-ERK和P-CREB分子水平的降低。同时应激也导致动物出现显著的抑郁样行为，应激组大鼠表现为快感缺乏、焦虑和活动性降低。而应激后氟西汀干预组大鼠的ERK-CREB信号系统活性水平显著高于应激组，此外，应激后氟西汀干预组大鼠的抑郁样行为明显少于应激组大鼠。这说明氟西汀提高了抑郁大鼠ERK-CREB信号系统的活性，减轻了抑郁大鼠的抑郁样行为。
该研究表明，氟西汀的干预能够逆转应激大鼠脑ERK-CREB信号通路的损伤，并缓解其抑郁症状，这提示ERK-CREB信号系统可能是氟西汀发挥抗抑郁作用的靶信号通路，并可能参与了抑郁行为的分子机制。但要证明ERK-CREB信号系统损伤是否与抑郁行为之间存在因果关系，尚需进一步的研究。（生物谷Bioon.com）
生物谷推荐原始出处：
Neurobiol Dis. 2008 Aug;31(2):278-85.
Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress.
Qi X, Lin W, Li J, Li H, Wang W, Wang D, Sun M.
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Science, Beijing, 100101, China.
Our previous research indicates that the extracellular signal-regulated kinase (ERK)-cyclic AMP-responsive-element-binding protein (CREB) signal system may be involved in the molecular mechanism of depression. The present study further investigated the effect of antidepressant fluoxetine on the ERK-CREB signal system and the depressive-like behaviors in rats. Fluoxetine was administrated to either naive rats or stressed rats for 21 days. The results showed that chronic forced swim stress induced depressive-like behaviors and decreased the levels of P-ERK2, P-CREB, ERK1/2 and CREB in hippocampus and prefrontal cortex. Fluoxetine alleviated the depressive-like behaviors and reversed the disruptions of the P-ERK2 and P-CREB in stressed rats. Fluoxetine also exerted mood-elevating effect and increased the levels of the P-ERK2 and P-CREB in naive rats. These results suggest that the ERK-CREB signal system may be the targets of the antidepressant action of fluoxetine and participate in the neuronal mechanism of depression.
