Department of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Yanta District, Xi'an, 710061, Shanxi, China.
Center Laboratory, Heze Medical College, Heze, 274000, Shandong, China.
Neurochem Res. 2017 Dec;42(12):3456-3464. doi: 10.1007/s11064-017-2393-7. Epub 2017 Oct 10.
This study is to determine the role and mechanism of hippocampal acetylation in prenatal stress (PS) induced depression-like behavior of male offspring rats. PS-induced depression rat model was established. Sucrose preference and forced swim test were used to observe the behavior changes of male offspring rats. Hippocampal acetylation was induced by Trichostatin A injection. Quantitative real-time PCR and Western blot were used to determine the changes of AMPARs in acetylated hippocampus. The behavioral tests proved that AMPA was involved in the PS-induced depression-like behavior in offspring rats. Hippocampal acetylation significantly increased the preference to sucrose of PS-induced offspring rats and reduced the immobile time in forced swimming test, suggesting that acetylation could improve PS-induced depression-like behaviors. In addition, PS inhibited the expression levels of GluA1-3 subunits of AMPARs in the offspring hippocampus, while Hippocampal acetylation could reverse this effect by increasing GluA1-3 expression. PS-induced reduction of GluA1-3 subunits of AMPARs may be an important potential mechanism of offspring depression. Hippocampal acetylation may improve PS-induced offspring depression-like behavior through the enhanced expression of AMPARs (GluA1-3 subunits).
本研究旨在确定海马乙酰化在产前应激（PS）诱导雄性子代大鼠抑郁样行为中的作用和机制。建立 PS 诱导的抑郁大鼠模型。通过蔗糖偏好和强迫游泳试验观察雄性子代大鼠的行为变化。用 Trichostatin A 注射诱导海马乙酰化。采用定量实时 PCR 和 Western blot 检测乙酰化海马中 AMPARs 的变化。行为学测试证实 AMPA 参与了 PS 诱导的子代大鼠抑郁样行为。海马乙酰化显著增加了 PS 诱导子代大鼠对蔗糖的偏好，并减少了强迫游泳试验中的不动时间，提示乙酰化可以改善 PS 诱导的抑郁样行为。此外，PS 抑制了子代海马中 AMPARs 的 GluA1-3 亚基的表达水平，而海马乙酰化可以通过增加 GluA1-3 的表达来逆转这种作用。PS 诱导的 AMPARs（GluA1-3 亚基）减少可能是子代抑郁的一个重要潜在机制。海马乙酰化可能通过增强 AMPARs（GluA1-3 亚基）的表达来改善 PS 诱导的子代抑郁样行为。
