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Prenatal Stress Impairs Postnatal Learning and Memory Development via Disturbance of the cGMP–PKG Pathway and Oxidative Phosphorylation in the Hippocampus of Rats
Frontiers in Molecular Neuroscience ( IF 4.8 ) Pub Date : 2020-08-03 , DOI: 10.3389/fnmol.2020.00158
Yu-jie Li , Li-ping Yang , Jun-lin Hou , Xin-min Li , Lei Chen , Jiang-hui Zhu , Qi-yang Wang , Gai Li , Pei-yuan Zhao , Xi-hong Liu , Zhan-jiang Shi

Clinical and animal studies have found that prenatal stress can lead to pathological changes in embryos and fetuses. However, the mechanisms through which this occurs have not been made clear. In the present study, pregnant rats were subjected to chronic psychological stress during gestational days using an improved communication box system, and the changes in behavioral performance and proteins in the hippocampus of offspring were analyzed. It was found that prenatal stress caused postnatal growth retardation and impairment in spatial learning and memory. Furthermore, in isobaric tags for relative and absolute quantitation-based proteomics analyses, 158 significantly differentially expressed proteins (DEPs) were found between the two groups. Further analyses showed that these DEPs are involved in different molecular function categories and participate in several biological processes, such as energy metabolism, learning or memory, and synaptic plasticity. Moreover, the enrichment of pathways showed that the learning and memory impairment was primarily connected with the cyclic guanosine monophosphate–protein kinase G (cGMP–PKG) pathway and oxidative phosphorylation. At the same time, the cGMP level and the expression of PKG protein were significantly decreased, and the neuronal mitochondria appeared to have a swollen and irregular shape in the hippocampus of offspring of stressed rats. These results suggest that the chronic psychological stress that pregnant rats were subjected to during gestational days may have impaired the spatial learning and memory of offspring. This affected the hippocampal oxidative phosphorylation and inhibited the cGMP–PKG pathway.



中文翻译:

产前应激通过干扰大鼠海马中cGMP-PKG途径和氧化磷酸化而损害产后学习和记忆发育。

临床和动物研究发现,产前压力可导致胚胎和胎儿的病理变化。但是,尚不清楚发生这种情况的机制。在本研究中,妊娠大鼠在孕期使用改良的通讯盒系统承受慢性心理压力,并分析了其行为表现和后代海马蛋白质的变化。研究发现,产前压力导致产后发育迟缓,并损害空间学习和记忆能力。此外,在基于相对定量和绝对定量的蛋白质组学分析的等压标签中,两组之间发现了158个显着差异表达的蛋白质(DEP)。进一步的分析表明,这些DEP参与了不同的分子功能类别,并参与了多个生物过程,例如能量代谢,学习或记忆以及突触可塑性。此外,途径的丰富表明,学习和记忆障碍主要与环鸟苷单磷酸-蛋白激酶G(cGMP-PKG)途径和氧化磷酸化有关。同时,应激大鼠后代的海马中cGMP水平和PKG蛋白的表达明显降低,神经元线粒体呈肿胀和不规则形状。这些结果表明,妊娠大鼠在妊娠期间遭受的慢性心理压力可能损害了后代的空间学习和记忆。

更新日期:2020-09-05
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