A large body of literature has demonstrated that prenatal stress (PS) can induce depression-like behavior in the offspring. However, the underlying mechanism remains largely unknown. CREB-regulated transcriptional coactivator 1(CRTC1) has recently been shown to involve in mood regulation. This research aims to investigate whether CRTC1 signaling was involved in the depression-like behavior of prenatally stressed offspring rats. Sucrose preference test (SPT), forced swimming test (FST) and open field test (OFT) were adopted to test the depression-like behavior in the male offspring rats, and CRTC1 signaling was measured. The results showed that there were significantly reduced sucrose intake in SPT and prolonged immobility time in FST in PS-exposure offspring rats. It was also found decreased levels of total CRTC1, nuclear CRTC1, calcineurin, brain-derived neurotrophic factor (BDNF) and c-fos, but increased cytoplasmic p-CRTC1 in the hippocampus (HIP) and prefrontal cortex (PFC) of the offspring rats. Furthermore, the mRNA level of CRTC1, calcineurin, BDNF, c-fos were down-regulated. Abnormal expression of CRTC1 signaling could be alleviated by fluoxetine treatment. In conclusion, our research indicated that the aberration of CRTC1 expression and/or phosphorylation activity might play a vital role in PS-induced depression-like behavior of offspring rats.

大量文献表明，产前压力 (PS) 会导致后代出现抑郁样行为。然而，潜在的机制在很大程度上仍然未知。CREB ​​调节的转录共激活因子 1（CRTC1）最近已被证明参与情绪调节。本研究旨在调查 CRTC1 信号是否与产前应激后代大鼠的抑郁样行为有关。采用蔗糖偏好试验（SPT）、强迫游泳试验（FST）和旷场试验（OFT）测试雄性后代大鼠的抑郁样行为，并测量CRTC1信号。结果表明，暴露于 PS 的后代大鼠 SPT 中蔗糖摄入量显着减少，FST 中不动时间延长。还发现总 CRTC1、核 CRTC1、钙调神经磷酸酶、脑源性神经营养因子 (BDNF) 和 c-fos，但增加了后代大鼠海马体 (HIP) 和前额叶皮层 (PFC) 中的细胞质 p​​-CRTC1。此外，CRTC1、钙调神经磷酸酶、BDNF、c-fos 的 mRNA 水平被下调。氟西汀治疗可以减轻 CRTC1 信号的异常表达。总之，我们的研究表明，CRTC1 表达和/或磷酸化活性的异常可能在 PS 诱导的子代大鼠抑郁样行为中起重要作用。