Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, China.
Brain Res Bull. 2013 Oct;99:1-8. doi: 10.1016/j.brainresbull.2013.08.003. Epub 2013 Sep 1.
A number of studies reveal that prenatal stress (PS) may induce an increased vulnerability to depression in offspring. Some evidences indicate that extracellular signal-regulated kinase (ERK)-cyclic AMP responsive element binding protein (CREB) signal system may play an important role in the molecular mechanism of depression. In the present study, we examined the effects of prenatal restraint stress on depression-like behavior in one-month offspring Sprague-Dawley rats and expression of ERK2, CREB, B-cell lymphoma-2 (Bcl-2) mRNA in the hippocampus, prefrontal cortex and striatum to explore the potential role of ERK-CREB pathway in mediating the behavioral effects of PS exposure. Our findings demonstrated that PS increased immobility time in forced swimming test and decreased expression of ERK2, CREB, Bcl-2 mRNA in the hippocampus and prefrontal cortex of juvenile offspring rats except for CREB in hippocampus of male offspring. Changes induced by PS were partly prevented by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. These findings suggested that the ERK-CREB system might be related with the depression-like behavior in juvenile offspring rats subjected to PS, in which NMDA receptors might be involved.
一些研究表明，产前应激（PS）可能会增加后代易患抑郁症的风险。一些证据表明，细胞外信号调节激酶（ERK）-环腺苷酸反应元件结合蛋白（CREB）信号系统可能在抑郁症的分子机制中发挥重要作用。在本研究中，我们检查了产前束缚应激对一个月大的 Sprague-Dawley 幼鼠抑郁样行为的影响，以及 ERK2、CREB、B 细胞淋巴瘤-2（Bcl-2）mRNA 在海马体、前额叶皮层和纹状体中的表达，以探讨 ERK-CREB 通路在介导 PS 暴露的行为效应中的潜在作用。我们的研究结果表明，PS 增加了幼鼠在强迫游泳试验中的不动时间，并降低了海马体和前额叶皮层中 ERK2、CREB、Bcl-2 mRNA 的表达，但雄性幼鼠海马体中的 CREB 除外。PS 引起的变化部分被 NMDA 受体拮抗剂 MK-801 阻止。这些发现表明，ERK-CREB 系统可能与 PS 引起的幼鼠抑郁样行为有关，其中 NMDA 受体可能参与其中。
