Translocator protein 18 kDa (TSPO) is mainly distributed in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. It mediates cholesterol transportation across the phospholipid membrane, which is a prerequisite for neurosteroid synthesis. Though the ligand of TSPO has clinical value in the diagnosis and treatment of neuropsychiatric disorders, the pharmacological study of TSPO for anti-postpartum depression has not been reported. In this study, the classical method of reproductive hormone withdrawal was used to construct a rat model of postpartum depression (PPD). The effect of YL-IPA08, a new ligand compound of TSPO, on PPD was evaluated using multiple behavioral tests at progressive time points. Additionally, real-time quantitative PCR, Western-blotting and an enzyme linked immunosorbent assay were conducted to elucidate the potential molecular mechanism of such effect. We report that the levels of TSPO and neurosteroids in the hippocampus and prefrontal cortex were significantly decreased in PPD rats compared to healthy controls. After 3 weeks of drug treatment, the levels of TSPO and neurosteroids in the hippocampus of PPD rats were increased, and anxiety and depressive like behaviors were alleviated. Meanwhile, compared with sertraline treatment, a positive control in this study, YL-IPA08 treatment had a shorter onset time. Our results suggest that the anxiolytic and anti-depressive activity of YL-IPA08 has significant value in the treatment of PPD and that TSPO may be a potential new target for the treatment of PPD.

中文翻译：

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易位蛋白（18 kDa）配体YL-IPA08在产后抑郁模型中的抗焦虑和抗抑郁作用。

转运蛋白18 kDa（TSPO）主要分布在中枢神经系统和周围神经系统的类固醇合成细胞的线粒体外膜中。它介导胆固醇通过磷脂膜的运输，这是神经甾体合成的先决条件。尽管TSPO的配体在神经精神疾病的诊断和治疗中具有临床价值，但尚未报道TSPO抗产后抑郁的药理研究。在这项研究中，经典的生殖激素戒断方法被用于构建产后抑郁症（PPD）的大鼠模型。使用渐进时间点的多项行为测试评估了TSPO的新配体化合物YL-IPA08对PPD的影响。此外，实时定量PCR 进行了蛋白质印迹和酶联免疫吸附试验，以阐明这种作用的潜在分子机制。我们报告说，与健康对照组相比，PPD大鼠海马和前额叶皮层中TSPO和神经甾体的水平明显降低。药物治疗3周后，PPD大鼠海马中的TSPO和神经甾体水平增加，焦虑和抑郁样行为得到缓解。同时，与本研究的阳性对照舍曲林治疗相比，YL-IPA08治疗的起病时间更短。我们的结果表明，YL-IPA08的抗焦虑和抗抑郁活性在PPD的治疗中具有重要价值，而TSPO可能是治疗PPD的潜在新靶标。