通过肠道-生殖系神经信号传导改善秀丽隐杆线虫肠道胀气依赖性回避行为

IF 5 1区 医学 Q1 NEUROSCIENCES
Siyi Lin, Huangjie Fu, Hanxiao Wang, Yingying Xu, Yu Zhao, Shiyu Du, Jiale Wei, Ping Qiu, Senlin Shi, Changyu Li, Thomas Efferth, Chunlan Hong
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引用次数: 0

摘要

目的研究自由漫游剂(FAEW)对热致杀大肠杆菌(Escherichia coli)致避避行为的保护作用,并探讨其机制。方法首先观察FAEW对小鼠回避行为、生存、神经内分泌信号基因表达和肠道胀气的影响。通过监测H4K8ac表达和par-5 RNAi动物和glp-1(e2141)突变体的回避行为来评估FAEW对肠道种系神经信号传导的影响。通过rna测序分析潜在的信号通路。最后,使用daf-16(mu86)突变体和获救动物检测回避行为。结果少数延迟回避行为。fafew可显著下调神经内分泌信号通路基因表达,减轻秀丽隐杆线虫肠道胀气。FAEW处理后,种系中H4K8ac和par-5水平显著下降,FAEW无法影响par-5 RNAi动物和glp-1(e2141)突变体的回避行为。FAEW对daf-16(mu86)突变体的回避行为的影响减弱,但在daf-16获救动物中恢复。少数已被观察到恢复daf-16水平。结论fafew通过下调H4K8ac蛋白表达和激活DAF-16来抑制秀丽隐杆线虫的逃避行为。这项研究提供了关键的实验证据,支持fafew作为一种有希望的候选药物,可以预防与PTSD相关的回避行为。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Free and Easy Wanderer Ameliorates Intestinal Bloating-Dependent Avoidance Behavior of Caenorhabditis elegans Through Gut-Germline-Neural Signaling

Free and Easy Wanderer Ameliorates Intestinal Bloating-Dependent Avoidance Behavior of Caenorhabditis elegans Through Gut-Germline-Neural Signaling

Purpose

The aim of this study was to investigate the protective effect of Free and Easy Wanderer (FAEW) on the avoidance behavior induced by feeding Heat-Killed Escherichia coli, and to elucidate the underlying mechanisms.

Methods

Initially, the effects of FAEW on avoidance behavior, survival, neuroendocrine signaling gene expression, and intestinal bloating were examined. The impact of FAEW on gut-germline-neural signaling was assessed by monitoring H4K8ac expression and the avoidance behavior of par-5 RNAi animals and glp-1(e2141) mutants. RNA-sequencing was conducted to analyze potential signaling pathways. Finally, avoidance behavior was examined using daf-16(mu86) mutants and the rescued animals.

Results

FAEW delayed avoidance behavior. FAEW significantly downregulated gene expression in the neuroendocrine signaling pathway and alleviated intestinal bloating of C. elegans. The levels of H4K8ac and par-5 in the germline decreased significantly with FAEW's treatment, and FAEW failed to affect the avoidance behavior of par-5 RNAi animals and glp-1(e2141) mutants. FAEW's effect on avoidance behavior diminished in daf-16(mu86) mutants but was restored in daf-16 rescued animals. FAEW has been observed to restore daf-16 levels.

Conclusion

FAEW protects against avoidance behavior of C. elegans through downregulating H4K8ac protein expression and activating DAF-16. This study provides crucial experimental evidence supporting FAEW as a promising candidate for protecting against avoidance behavior associated with PTSD.

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来源期刊
CNS Neuroscience & Therapeutics
CNS Neuroscience & Therapeutics 医学-神经科学
CiteScore
7.30
自引率
12.70%
发文量
240
审稿时长
2 months
期刊介绍: CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.
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