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,Cell Biology and Toxicology

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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
Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2021-06-29 , DOI: 10.1007/s10565-021-09621-0
Shuai Zhang ₁ , Shuwei Hu ₁ , Wanting Dong ₁ , Songqiang Huang ₁ , Zhexiao Jiao ₁ , Zewen Hu _{1,

2} , Shiyun Dai ₁ , Yiwen Yi ₁ , Xiaohan Gong ₁ , Ke Li ₂ , Hui Wang _{1,

3} , Dan Xu _{1,

3}

Affiliation

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 abstract

Intrauterine 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

中文翻译：

产前地塞米松暴露通过宫内编程激活海马 PV 中间神经元中的 NRG1-ErbB4 信号传导诱导雄性子代大鼠的焦虑和抑郁样行为

地塞米松是临床常用的合成糖皮质激素。作为一种可以穿过胎盘屏障促进胎肺成熟的化合物，地塞米松广泛用于有早产风险的孕妇。然而，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，我们观察了先前产前接触过地塞米松（PDE）的成年大鼠后代的焦虑和抑郁样行为变化以及海马神经元的过度兴奋性。观察到的变化与小清蛋白中间神经元的子宫内损伤有关。神经调节蛋白 1 (NRG1)-Erb-b2 受体酪氨酸激酶 4 (ErbB4) 信号的程序性变化是 PDE 后代海马小清蛋白中间神经元损伤的关键。PDE 后代的焦虑和抑郁样行为、NRG1-ErbB4 信号传导激活以及小清蛋白中间神经元的损伤在慢性应激后加剧。NRG1-ErbB4 信号传导的干预有助于改善地塞米松介导的小清蛋白中间神经元损伤。这些结果表明，PDE 可能通过 NRG1-ErbB4 信号的程序性激活，导致雄性大鼠后代出现焦虑和抑郁样行为变化，导致小清蛋白中间神经元损伤和海马体过度活跃。