Division of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Department of Genetics, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
Neuroscience. 2018 Jun 15;381:138-148. doi: 10.1016/j.neuroscience.2018.03.043. Epub 2018 Apr 4.
Increasing evidence has shown that prenatal stress (PS) could cause depression-like behavior in the offspring, which is sex-specific. However, the underlying mechanisms remain to be elucidated. This study is to investigate the involvement of tryptophan hydroxylase 2 (Tph2) H3K9 acetylation (H3K9ac) modification on PS-induced depression-like behavior in juvenile offspring rats (JOR). PS models were established, with or without trichostatin A (TSA) treatment. Animal behavior was assessed by the sucrose preference test (SPT) and forced swimming test (FST). The mRNA and protein expression levels of TPH2 in the dorsal raphenucleus (DRN), hippocampus, and prefrontal cortex were detected with quantitative real-time PCR and Western blot analysis, respectively. The Tph2 H3K9ac levels in the hippocampus were also analyzed. SPT and FST showed significantly reduced sucrose preference and significantly prolonged immobility in PS-induced male juvenile offspring rats (MJOR). Moreover, the mRNA and protein expression levels of TPH2 in the DRN and hippocampus were significantly declined, while the hippocampal Tph2 H3K9ac levels were significantly declined in the PS-induced MJOR. Furthermore, the PS-induced effects in MJOR could be reversed by the microinjection of TSA. However, no significant effects were observed for the female juvenile offspring rats (FJORs). In conclusion, our results showed that the Tph2 H3K9ac modification is only involved in PS-induced depression-like behavior in MJOR, in a sex-specific manner. These findings might contribute to the understanding of the disease pathogenesis and clinical treatment in future.
越来越多的证据表明，产前应激（PS）可导致后代出现抑郁样行为，且具有性别特异性。然而，其潜在机制仍有待阐明。本研究旨在探讨色氨酸羟化酶 2（Tph2）H3K9 乙酰化（H3K9ac）修饰是否参与 PS 诱导的幼年雄性大鼠（JOR）抑郁样行为。建立 PS 模型，并进行曲古抑菌素 A（TSA）处理。通过蔗糖偏好试验（SPT）和强迫游泳试验（FST）评估动物行为。采用实时定量 PCR 和 Western blot 分析检测中缝背核（DRN）、海马和前额叶皮质中 TPH2 的 mRNA 和蛋白表达水平，分析海马中 Tph2 H3K9ac 水平。SPT 和 FST 显示 PS 诱导的雄性幼年大鼠（MJOR）的蔗糖偏好显著降低，不动时间显著延长。此外，DRN 和海马中 TPH2 的 mRNA 和蛋白表达水平显著下降，而 PS 诱导的 MJOR 中海马 Tph2 H3K9ac 水平显著下降。此外，TSA 的微注射可逆转 PS 诱导的 MJOR 效应。然而，PS 对雌性幼年大鼠（FJORs）没有明显影响。总之，我们的结果表明，Tph2 H3K9ac 修饰仅参与 PS 诱导的雄性幼年大鼠抑郁样行为，具有性别特异性。这些发现可能有助于理解未来的疾病发病机制和临床治疗。
