左归丸通过雌激素受体ERα甲基化途径改善脑衰老小鼠的学习和记忆能力

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Yang Huang, Lili Zhong, Jing Yang, Qiaomei Dai, Li Zhao, Mengdi Zhang, Hong Liu
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引用次数: 0

摘要

引言性激素是维持大脑功能和保护大脑的重要因素。最新研究表明,脑衰老过程中神经元的损伤可能与雌激素受体α(ERα)的甲基化有关。然而,左归丸(ZGW)在脑衰老ERα DNA甲基化和神经元修复中的作用机制仍然未知:材料和方法:采用D-半乳糖诱导的卵巢切除小鼠作为衰老模型。通过阴道细胞涂片检测小鼠发情周期的变化。进行动物行为测试,包括莫里斯水迷宫(MWM)和新物体识别(NOR)测试。采用苏木精-伊红(HE)和Nissl染色法评估海马神经发生。酶联免疫吸附试验(ELISA)检测了5-甲基胞嘧啶甲基化水平,免疫组化(IHC)和免疫印迹(WB)实验评估了ZGW处理后ERα/DNA甲基转移酶1(DNMT1)的表达。最后,进行了亚硫酸氢盐测序PCR(BSP)分析,以确定ZGW处理前后D-gal诱导的衰老神经元中甲基化差异表达的雌激素受体1(ESR1)基因:结果:我们发现ERα甲基化参与了ZGW延缓脑衰老的过程。从机理上讲,ZGW能改善脑衰老小鼠的学习记忆能力,降低血清中5-甲基胞嘧啶(5-mc)的表达,增加ERα的含量,抑制DNMT1的表达,并显著降低ESRI基因的甲基化表达:我们的数据表明,ZGW 可延缓 D-gal 诱导的小鼠脑衰老。这些结果表明,ZGW 对衰老有益,可用于衰老过程中的神经元保护。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Zuogui Pills Improve the Learning and Memory Ability of Brain-Aging Mice through the Estrogen Receptor ERα Methylation Pathway.

Introduction: Sex hormones are important factors in maintaining brain function and acting as brain protectors. Recent research suggests that neuronal damage in brain aging may be linked to the methylation of the estrogen receptor α (ERα). However, the mechanism of Zuogui Pills (ZGW) in brain-aging ERα DNA methylation and neuronal repair remains unknown.

Materials and methods: D-galactose-induced ovary removal mice were used as a model of aging. Changes in estrous cycle were detected in mice by vaginal cell smear. Animal behavior tests, including the Morris water maze (MWM) and new object recognition (NOR) test, were conducted. Hematoxylin-eosin (HE) and Nissl-staining were carried out to assess hippocampal neurogenesis. Enzyme-linked immunosorbent assay (ELISA) was performed for 5- methylcytosine methylation levels, and immunohistochemistry (IHC) and western blotting (WB) experiments were performed to assess ERα/DNA methyltransferase 1 (DNMT1) expression after ZGW treatment. Finally, bisulfite sequencing PCR (BSP) analysis was performed to identify methylated differentially expressed estrogen receptor 1 (ESR1) gene in D-gal-induced senescent neurons before and after ZGW treatment.

Results: We found that ERα methylation was involved in the delayed brain ageing process of ZGW. Mechanistically, ZGW can improve the learning and memory ability of brain-aging mice, reduce the expression of 5-methylcytosine (5-mc) in serum, increase the amount of ERα, inhibit the expression of DNMT1, and significantly reduce methylated expression of the ESRI gene.

Conclusion: Our data suggested that ZGW slowed down D-gal-induced brain aging in mice, and these results showed that ZGW is beneficial for aging. It may be used for neuronal protection in aging.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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