中科院心理所林文娟和亓?xí)喳惖葘＜覟檫M(jìn)一步研究ERK-CREB信號(hào)系統(tǒng)在抑郁行為中的可能作用,，他們探討了抗抑郁藥氟西汀(fluoxetine)對(duì)大鼠腦ERK-CREB信號(hào)系統(tǒng)及抑郁樣行為的作用。他們前期的研究工作提示,，細(xì)胞外信號(hào)調(diào)節(jié)激酶(ERK)和cAMP反應(yīng)元件結(jié)合蛋白(CREB)信號(hào)系統(tǒng)可能與抑郁行為的分子機(jī)制有關(guān),。
氟西汀是一種臨床廣泛應(yīng)用的抗抑郁藥物,，通過抑制中樞神經(jīng)系統(tǒng)突觸間‘隙5-羥色胺’的再攝取發(fā)揮臨床療效。該研究將實(shí)驗(yàn)大鼠分為對(duì)照組,、氟西汀組,、應(yīng)激組和應(yīng)激后氟西汀干預(yù)組。研究結(jié)果表明,，21天的強(qiáng)迫游泳應(yīng)激顯著降低了應(yīng)激組大鼠在海馬和前額葉皮質(zhì)ERK-CREB信號(hào)系統(tǒng)的活性水平,，主要體現(xiàn)為應(yīng)激大鼠海馬和前額葉皮質(zhì)P-ERK和P-CREB分子水平的降低。同時(shí)應(yīng)激也導(dǎo)致動(dòng)物出現(xiàn)顯著的抑郁樣行為,，應(yīng)激組大鼠表現(xiàn)為快感缺乏,、焦慮和活動(dòng)性降低。而應(yīng)激后氟西汀干預(yù)組大鼠的ERK-CREB信號(hào)系統(tǒng)活性水平顯著高于應(yīng)激組,，此外,，應(yīng)激后氟西汀干預(yù)組大鼠的抑郁樣行為明顯少于應(yīng)激組大鼠。這說明氟西汀提高了抑郁大鼠ERK-CREB信號(hào)系統(tǒng)的活性,，減輕了抑郁大鼠的抑郁樣行為,。
該研究表明，氟西汀的干預(yù)能夠逆轉(zhuǎn)應(yīng)激大鼠腦ERK-CREB信號(hào)通路的損傷,，并緩解其抑郁癥狀,，這提示ERK-CREB信號(hào)系統(tǒng)可能是氟西汀發(fā)揮抗抑郁作用的靶信號(hào)通路，并可能參與了抑郁行為的分子機(jī)制,。但要證明ERK-CREB信號(hào)系統(tǒng)損傷是否與抑郁行為之間存在因果關(guān)系,，尚需進(jìn)一步的研究。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
