Cellular and Molecular Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Sci Rep. 2019 Feb 4;9(1):1305. doi: 10.1038/s41598-018-38085-2.
Prenatal stress (PNS) has gained attention with regard to its impact on hippocampal neurogenesis in neonates which serves as a risk factor for postnatal neurodevelopmental deficits. Evidences from animal models have suggested that depression responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal response via cortisol, is responsible for critical neurodevelopmental deficits in the offspring which is transduced due to gestational stress. But knowledge in the area of assessing the effects of maternal chronic unpredictable mild stress (CUMS) on neurogenesis and expression of some key signaling molecules in the offsprings are limited. We have used Wistar rats to induce PNS in offsprings by maternal CUMS during pregnancy. Prefrontal cortex (PFC) and hippocampus were assessed for biomarkers of oxidative stress, neurogenesis, neurodevelopmental signaling molecules and DNA damage in the male Wister offsprings. Our investigations resulted in sufficient evidences which prove how maternal psychological stress has widespread effect on the fetal outcomes via major physiological alteration in the antioxidant levels, neurogenesis, signaling molecules and DNA damage. PNS leads to the upregulation of GSK-3β which in turn inhibited mRNA and protein expressions of sonic hedgehog (SHH), β-catenin, Notch and brain derived neurotrophic factor (BDNF). The study explored multifaceted signaling molecules especially, GSK-3β responsible for crosstalks between different neurodevelopmental molecules like SHH, Notch, BDNF and β-catenin affecting neurodevelopment of the offsprings due to PNS.
产前应激（Prenatal stress，PNS）对新生儿海马神经发生的影响引起了关注，因为它是导致产后神经发育缺陷的一个风险因素。动物模型的证据表明，抑郁反应性下丘脑-垂体-肾上腺（Hypothalamic-pituitary-adrenal，HPA）轴及其通过皮质醇的激素反应，负责子代为妊娠期应激而发生的关键神经发育缺陷。但是，评估母体慢性不可预测轻度应激（Chronic unpredictable mild stress，CUMS）对子代神经发生和某些关键信号分子表达的影响的相关知识是有限的。我们使用 Wistar 大鼠通过母体妊娠期 CUMS 诱导后代 PNS。我们评估了雄性 Wister 后代的前额叶皮层（Prefrontal cortex，PFC）和海马中的氧化应激、神经发生、神经发育信号分子和 DNA 损伤的生物标志物。我们的研究提供了充分的证据，证明了母体心理应激如何通过抗氧化水平、神经发生、信号分子和 DNA 损伤的主要生理改变对胎儿结局产生广泛影响。PNS 导致 GSK-3β的上调，进而抑制 sonic hedgehog（SHH）、β-catenin、Notch 和脑源性神经营养因子（brain derived neurotrophic factor，BDNF）的 mRNA 和蛋白质表达。该研究探索了多方面的信号分子，特别是 GSK-3β，它负责不同神经发育分子之间的串扰，如 SHH、Notch、BDNF 和β-catenin，从而影响 PNS 后代的神经发育。
