Chronic fluoxetine induces region-specific changes in translation factor eIF4E and eEF2 activity in the rat brain
Chronic fluoxetine induces region-specific changes in translation factor eIF4E and eEF2 activity in the rat brain
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DOI：
10.1111/j.1460-9568.2006.04817.x
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发表时间：
2006-05-01
影响因子：
3.4
通讯作者：
Bramham, Clive R.
中科院分区：
文献类型：
--
作者：
Dagestad, Grethe;Kuipers, Sjoukje D.;Bramham, Clive R.
慢性抗抑郁药物治疗后观察到的治疗起效延迟尚不清楚。虽然目前的理论强调对基因转录的影响，但抗抑郁药物对翻译控制途径的可能影响尚未探讨。我们研究了选择性β-肾上腺素能再摄取抑制剂氟西汀对mRNA翻译的两个主要决定因素，真核细胞起始因子4 E（eIF 4 E）和真核细胞延伸因子2（eEF 2）的调节作用。慢性氟西汀治疗诱导大鼠前额叶皮层、海马和齿状回eEF 2（Thr 56）过度磷酸化。相比之下，eIF 4 E（Ser 209）的磷酸化，特别是在齿状回中观察到。急性百忧解治疗对翻译因子活性没有影响。这些发现表明，翻译的区域特异性调节有助于抗抑郁药物如氟西汀的延迟作用。
The delayed therapeutic onset observed in response to chronic antidepressant drug treatment is little understood. While current theories emphasize effects on gene transcription, possible effects of antidepressant drugs on translation control pathways have not been explored. We examined the effect of the selective serotonergic reuptake inhibitor fluoxetine on regulation of two major determinants of mRNA translation, eukaryotic initiation factor 4E (eIF4E) and eukaryotic elongation factor 2 (eEF2). Chronic fluoxetine treatment induced hyperphosphorylation of eEF2 (Thr56) in prefrontal cortex, hippocampus and dentate gyrus of rats. By contrast, phosphorylation of eIF4E (Ser209) was observed specifically in the dentate gyrus. Acute fluoxetine treatment had no effect on translational factor activity. These findings suggest that region-specific regulation of translation contributes to the delayed action of antidepressant drugs such as fluoxetine.