Expression of microRNA induced by postoperative delirium-like behavior is associated with long-term default mode network disruption: Sequencing and a secondary analysis of resting-state fMRI data

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-09-24 DOI:10.1111/cns.70038

Yang Liu, Huiru Feng, Huiqun Fu, Binbin Nie, Tianlong Wang

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Abstract

Aims

Resting state functional magnetic resonance imaging (rs-fMRI) has been widely used in studying default mode network (DMN) changes in postoperative delirium (POD). Reproducibility and interpretability of the analyzing results remain insufficiently studied.

Methods

Delirium-like behavior was induced by tibial fixation surgery under isoflurane anesthesia. Firstly, we evaluated delirium-like behavior and inflammatory responses in hippocampus and systemic level. Then the expressions of microRNA (miRNA) and target gene were sequenced and validated. Afterwards the functional connectivity (FC) in DMN was analyzed. Finally, results were correlated with DMN changes.

Results

POD-like behavior caused significant changes of miR-34b-5p, miR-328-5p, and miR-3505 in miRNA level and Nos1, Tubb3, and Gys1 in the gene level. The FC in left and right hippocampus (L-Hip and R-Hip) and right auditory cortex (R-AC) was found significantly changed. Significant correlations were found in FC_L-Hip/R-AC and FC_R-Hip/R-AC for miR-34b-5p and miR-3505, as well as Nos1 and Tubb3. For miR-328-5p, no significant correlations were found.

Conclusion

Our study demonstrates that POD-like behavior induced significant miRNA and gene expression changes were associated with hippocampus related long-term FC disruption in DMN. The results increased reproducibility and interpretability for standardized rs-fMRI data analysis, as well as providing potential targets for postoperative delirium treatment.

Abstract Image

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术后谵妄样行为诱导的微RNA表达与长期默认模式网络中断有关：静息态 fMRI 数据的测序和二次分析

目的静息状态功能磁共振成像（rs-fMRI）已被广泛用于研究术后谵妄（POD）中默认模式网络（DMN）的变化。但对分析结果的可重复性和可解释性的研究仍然不足。方法在异氟烷麻醉下进行胫骨固定手术，诱发谵妄样行为。首先，我们评估了谵妄样行为和海马及全身的炎症反应。然后对微小RNA（miRNA）和靶基因的表达进行测序和验证。然后分析了DMN的功能连接（FC）。最后，将结果与 DMN 变化相关联。结果 POD-like 行为导致 miRNA 水平上的 miR-34b-5p、miR-328-5p 和 miR-3505 以及基因水平上的 Nos1、Tubb3 和 Gys1 发生了显著变化。研究发现，左右海马（L-Hip 和 R-Hip）和右听觉皮层（R-AC）的 FC 发生了显著变化。在 FCL-Hip/R-AC 和 FCR-Hip/R-AC 中，miR-34b-5p、miR-3505 以及 Nos1 和 Tubb3 均有显著相关性。至于 miR-328-5p，则没有发现明显的相关性。结论我们的研究表明，POD 类行为诱导的显著 miRNA 和基因表达变化与 DMN 中与海马相关的长期 FC 干扰有关。研究结果提高了标准化 rs-fMRI 数据分析的可重复性和可解释性，并为术后谵妄治疗提供了潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.