Department of Anatomy and Neurobiology, Central South University School of Basic Medical Sciences, Changsha, Hunan, PR China; Department of Histology and Embryology, Basic Medical College of Xinjiang Medical University, Ürümqi, Xinjiang, PR China.
Center for Experimental Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Neurosci Res. 2019 Oct;147:9-16. doi: 10.1016/j.neures.2018.11.006. Epub 2018 Nov 16.
Accumulating evidence from preclinical and clinical studies indicates prenatal exposure to stress or excess glucocorticoids can affect offspring brain. HDAC2 is an important target of glucocorticoid. Here we detected HDAC2 expression in male offspring hippocampus from gestational restraint stressed rat during development and the relationship between HDAC2 expression and behaviors and neurogenesis in male offspring. Pregnant rats received restrained stress during the last week of pregnancy. Expressions of HDAC2 in offspring hippocampus were detected on postnatal 0 day (P0) and 60 days (P60). Neurogenesis was evaluated by Doublecortin (DCX) staining on P60. Anxiety-like behavior and cognition were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. We found that HDAC2 expression in the hippocampus of male prenatally stressed offspring (MPSO) was similar to the male control offspring on P0, but significantly lower on P60. Corresponding to the decreased expression of HDAC2 in MPSO hippocampus at P60, neurogenesis in the dentate gyrus of MPSO was significantly lower than the control male offspring. And MPSO also showed greater anxiety and poorer learning and memories abilities than control male offspring. These showed that HDAC2 could partly explain the effects of gestational stress on male offspring behaviors.
越来越多的临床前和临床研究证据表明，产前应激或皮质醇过量会影响后代的大脑。HDAC2 是皮质醇的一个重要靶点。本研究检测了发育过程中束缚应激孕鼠雄性子代海马中的 HDAC2 表达，并探讨了其与雄性子代行为和神经发生的关系。在妊娠最后一周对孕鼠进行束缚应激。分别于生后 0 天（P0）和 60 天（P60）检测子代海马中的 HDAC2 表达。P60 时通过 Doublecortin（DCX）染色评估神经发生。通过旷场实验、高架十字迷宫、新物体识别实验和 Barnes 迷宫检测焦虑样行为和认知。结果发现，与雄性对照组相比，雄性应激孕鼠（MPSO）子代 P0 时海马中的 HDAC2 表达相似，但 P60 时明显降低。与 MPSO 海马中 HDAC2 表达降低相对应，MPSO 齿状回神经发生明显低于对照组雄性子代。而且，MPSO 还表现出比对照组雄性子代更高的焦虑和更差的学习和记忆能力。这些表明，HDAC2 可以部分解释妊娠期应激对雄性子代行为的影响。
