GATA-binding protein 4 promotes neuroinflammation and cognitive impairment in Aβ_1-42 fibril-infused rats through small nucleolar RNA host gene 1/miR-361-3p axis.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2023-01-01 DOI:10.4103/cjop.CJOP-D-22-00057

Lidan Liu, Yanhui Peng, Wenping Liu, Jiajun Xu, Dali Li, Xiuwen Li

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Abstract

Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aβ_1-42 fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aβ_1-42 fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aβ_1-42 fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aβ_1-42 fibril-infused rats. Loss of GATA4 in Aβ_1-42 fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aβ_1-42 fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aβ_1-42 fibril-infused rats. In conclusion, silence of GATA4 ameliorated cognitive dysfunction and inhibited hippocampal inflammation and cell apoptosis through regulation of Sp1/SNHG1/miR-361-3p.

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gata结合蛋白4通过小核仁RNA宿主基因1/miR-361-3p轴促进Aβ1-42原纤维灌注大鼠的神经炎症和认知功能障碍。

代谢和免疫稳态失调的衰老刺激焦亡、神经炎症和细胞衰老，从而促进阿尔茨海默病的发病。gata结合蛋白4 (GATA4)作为一种转录因子在DNA损伤反应中起作用，并与神经炎症和细胞衰老有关。研究了GATA4在阿尔茨海默病中的作用。a - β1-42原纤维灌注大鼠海马GATA4升高。注射靶向GATA4的shRNA可减少Aβ1-42原纤维灌注大鼠的逃逸潜伏期，增加靶区时间和平台交叉次数。此外，敲低GATA4可改善Aβ1-42原纤维灌注大鼠海马的形态学改变，减少淀粉样斑块沉积。GATA4沉默抑制Aβ1-42原纤维灌注大鼠的神经炎症和细胞凋亡。注入Aβ1-42原纤维的大鼠GATA4缺失，降低特异性蛋白1 (Sp1)的表达，下调长链非编码RNA小核仁RNA宿主基因1 (SNHG1)，上调miR-361-3p。SNHG1缺失可改善Aβ1-42原纤维灌注大鼠的学习和记忆障碍。在Aβ1-42原纤维灌注大鼠中，Sp1的过表达减弱了GATA4沉默引起的逃避潜伏期减少、靶区时间增加和平台穿越次数增加。综上所述，GATA4沉默可通过调节Sp1/SNHG1/miR-361-3p改善认知功能障碍，抑制海马炎症和细胞凋亡。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.