脂肪量和肥胖相关蛋白调控与慢性脑灌注不足后空间认知功能障碍相关的 RNA 甲基化

IF 2.5 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Yanqing Wang , Zimei Wu , Yuyang He , Xiaoying Zeng , Zijuan Gu , Xianxi Zhou , Wenwen Si , Dongfeng Chen
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引用次数: 0

摘要

RNA 甲基化可从表观遗传学角度调控学习和记忆。然而,目前还不清楚 RNA 甲基化在血管性痴呆(VD)的病理生理学中是否起着关键作用。在这里,我们报告了在血管性痴呆模型的海马中,脂肪量和肥胖相关基因(FTO)(一种 RNA 去甲基化酶)的表达下调。通过预测和双荧光素酶报告验证研究,我们观察到 miRNA-711 在 VD 后上调,并能与 FTO mRNA 的 3′-非翻译区结合,在体外调控其表达。甲基化 RNA 免疫沉淀(MeRIP)-qPCR 检测和功能研究证实,Syn1 是 FTO 的一个重要靶基因。这表明 FTO 是 Syn1 的重要调控因子。通过抑制 miR-711 上调海马中的 FTO 可以缓解突触结合蛋白和体内突触恶化,而通过 miR-711 agomir 下调海马中的 FTO 则会导致突触恶化加剧。通过抑制 miR-711 上调 FTO 可以缓解 VD 模型大鼠的认知障碍,而通过 miR-711 下调 FTO 则会加重认知障碍。我们的研究结果表明,FTO是与慢性脑灌注不足后空间认知功能障碍相关的RNA甲基化机制的调节因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fat mass and obesity-associated protein regulates RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion

RNA methylation can epigenetically regulate learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of Vascular dementia (VD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus in models of VD. Through prediction and dual-luciferase reporters validation studies, we observed that miRNA-711 was upregulated after VD and could bind to the 3′-untranslated region of FTO mRNA and regulate its expression in vitro. Methylated RNA immunoprecipitation (MeRIP)-qPCR assay and functional study confirmed that Syn1 was an important target gene of FTO. This suggests that FTO is an important regulator of Syn1. FTO upregulation by inhibition of miR-711 in the hippocampus relieves synaptic association protein and synapse deterioration in vivo, whereas FTO downregulation by miR-711 agomir in the hippocampus leads to aggravate the synapse deterioration. FTO upregulation by inhibition of miR-711 relieves cognitive impairment of rats VD model, whereas FTO downregulation by miR-711 deteriorate cognitive impairment. Our findings suggest that FTO is a regulator of a mechanism underlying RNA methylation associated with spatial cognitive dysfunction after chronic cerebral hypoperfusion.

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来源期刊
Neuropeptides
Neuropeptides 医学-内分泌学与代谢
CiteScore
5.40
自引率
6.90%
发文量
55
审稿时长
>12 weeks
期刊介绍: The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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