Recent studies have suggested that CREB-regulated transcription coactivator 1 (CRTC1) plays a role in the pathophysiology of depression. Although imipramine is thought to prevent the reuptake of synaptic serotonin and norepinephrine, its antidepressant-like mechanisms remain elusive. In this study, the effects of imipramine on CRTC1 were studied in several models of depression, including the chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models. We examined whether repeated imipramine administration can reverse the effects of CRS, CUMS and CSDS on CRTC1 expression in both the hippocampus and medial prefrontal cortex (mPFC). Furthermore, genetic knockdown of CRTC1 by CRTC1-shRNA was used to determine whether CRTC1 is necessary for the antidepressant-like effects of imipramine in mice. Our results showed that imipramine reversed the down-regulating effects of CRS, CUMS and CSDS on CRTC1 expression in the mPFC but not the hippocampus, and that CRTC1-shRNA fully abolished the antidepressant-like actions of imipramine in mice. In conclusion, CRTC1 in the mPFC is involved in the antidepressant mechanism of imipramine.

最近的研究表明，CREB ​​调节的转录辅激活因子 1 (CRTC1) 在抑郁症的病理生理学中起作用。尽管丙咪嗪被认为可以阻止突触血清素和去甲肾上腺素的再摄取，但其抗抑郁样机制仍然难以捉摸。在这项研究中，丙咪嗪对 CRTC1 的影响在几种抑郁症模型中进行了研究，包括慢性束缚应激 (CRS)、慢性不可预测的轻度应激 (CUMS) 和慢性社交失败应激 (CSDS) 模型。我们检查了重复丙咪嗪给药是否可以逆转 CRS、CUMS 和 CSDS 对海马和内侧前额叶皮层 (mPFC) 中 CRTC1 表达的影响。此外，CRTC1-shRNA 对 CRTC1 的基因敲低用于确定 CRTC1 是否是丙咪嗪在小鼠中的抗抑郁样作用所必需的。我们的结果表明丙咪嗪逆转了 CRS、CUMS 和 CSDS 对 mPFC 中 CRTC1 表达的下调作用，但不能逆转海马体中的 CRTC1 表达，并且 CRTC1-shRNA 完全消除了丙咪嗪在小鼠中的抗抑郁样作用。总之，mPFC中的CRTC1参与丙咪嗪的抗抑郁机制。