Prenatal dexamethasone exposure induces anxiety- and depressive-like behavior of male offspring rats through intrauterine programming of the activation of NRG1-ErbB4 signaling in hippocampal PV interneurons
Prenatal dexamethasone exposure induces anxiety- and depressive-like behavior of male offspring rats through intrauterine programming of the activation of NRG1-ErbB4 signaling in hippocampal PV interneurons
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DOI：
10.1007/s10565-021-09621-0
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发表时间：
2021-06
影响因子：
6.1
通讯作者：
Shuai Zhang;Shuwei Hu;Wanting Dong;Songqian Huang;Zhexiao Jiao;Zewen Hu;Shiyun Dai;Yiwen Yi
中科院分区：
文献类型：
--
作者：
Shuai Zhang;Shuwei Hu;Wanting Dong;Songqian Huang;Zhexiao Jiao;Zewen Hu;Shiyun Dai;Yiwen Yi
地塞米松是临床上常用的合成糖皮质激素。地塞米松作为一种能够穿过胎盘屏障促进胎儿肺成熟的化合物，被广泛应用于有早产风险的孕妇。然而，在怀孕期间使用糖皮质激素会增加神经发育障碍的风险。在本研究中，我们观察了产前地塞米松暴露（PDE）的成年大鼠后代的焦虑和抑郁样行为改变和海马神经元的高兴奋性；观察到的变化与子宫内小白蛋白中间神经元的损伤有关。神经调节蛋白1 (NRG1)- erbb -b2受体酪氨酸激酶4 （ErbB4）信号的程序性改变是PDE后代海马小白蛋白中间神经元损伤的关键。慢性应激加重了PDE子代的焦虑和抑郁样行为、NRG1-ErbB4信号激活和小白蛋白中间神经元损伤。NRG1-ErbB4信号的干预有助于改善地塞米松介导的小白蛋白中间神经元损伤。这些结果表明，PDE可能通过程序性激活NRG1-ErbB4信号导致雄性大鼠后代焦虑和抑郁样行为改变，导致小白蛋白中间神经元损伤和海马过度活跃。地塞米松介导的神经调节蛋白1 (NRG1)- erbb -b2受体酪氨酸激酶4 （ERBB4）过度激活的子宫内编程介导雄性大鼠后代的焦虑和抑郁样行为
Dexamethasone is a commonly used synthetic glucocorticoid in the clinic. As a compound that can cross the placental barrier to promote fetal lung maturation, dexamethasone is extensively used in pregnant women at risk of premature delivery. However, the use of glucocorticoids during pregnancy increases the risk of neurodevelopmental disorders. In the present study, we observed anxiety- and depressive-like behavior changes and hyperexcitability of hippocampal neurons in adult rat offspring with previous prenatal dexamethasone exposure (PDE); the observed changes were related to in utero damage of parvalbumin interneurons. A programmed change in neuregulin 1 (NRG1)-Erb-b2 receptor tyrosine kinase 4 (ErbB4) signaling was the key to the damage of parvalbumin interneurons in the hippocampus of PDE offspring. Anxiety- and depressive-like behavior, NRG1-ErbB4 signaling activation, and damage of parvalbumin interneurons in PDE offspring were aggravated after chronic stress. The intervention of NRG1-ErbB4 signaling contributed to the improvement in dexamethasone-mediated injury to parvalbumin interneurons. These results suggested that PDE might cause anxiety- and depressive-like behavior changes in male rat offspring through the programmed activation of NRG1-ErbB4 signaling, resulting in damage to parvalbumin interneurons and hyperactivity of the hippocampus.Graphical abstractIntrauterine programming of neuregulin 1 (NRG1)-Erb-b2 receptor tyrosine kinase 4 (ERBB4) overactivation by dexamethasone mediates anxiety- and depressive-like behavior in male rat offspring