Role of Hippocampal Glutamatergic Synaptic Alterations in Sevoflurane-Induced Cognitive Dysfunction in Aged Mice

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-10-28 DOI:10.1111/cns.70093

Yixuan Niu, Guoying Liao, Zhengjie Miao, Jinnan Xu, Yanyong Cheng, Fan Wang, Chuanyu Qi, Tiannan Chen, Yi Gao, Lei Zhang, Hong Jiang, Jia Yan

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Abstract

Aims

Perioperative neurocognitive disorders (PND), including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), are common following anesthesia and surgery in older patients and significantly increase morbidity and mortality. However, the underlying mechanism of PND is unclear. Our study aims to analyze the differentially expressed genes (DEGs) in excitatory neurons and investigate the role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice.

Methods

We performed single-nucleus RNA sequencing (snRNA-seq) technology to examine the alterations of excitatory neurons in hippocampus induced by sevoflurane in aged mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed in excitatory neurons. At last, immunofluorescence staining was used to validate sevoflurane-induced alternation of glutamatergic synapses in the hippocampus of aged mice.

Results

This study demonstrates that DEGs in excitatory neurons are associated with reduction of glutamatergic synapses and cognitive dysfunction. After immunofluorescence staining validation, we also confirmed that sevoflurane anesthesia decreased the density of glutamatergic synapses in the hippocampus of aged mice.

Conclusions

Our findings demonstrated a key role of hippocampal glutamatergic synaptic alterations in sevoflurane-induced cognitive dysfunction in aged mice.

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海马谷氨酸能突触改变在七氟醚诱导的老年小鼠认知功能障碍中的作用

目的：围手术期神经认知障碍（PND），包括术后谵妄（POD）和术后认知功能障碍（POCD），是老年患者麻醉和手术后的常见病，会显著增加发病率和死亡率。然而，PND 的内在机制尚不清楚。我们的研究旨在分析兴奋性神经元中的差异表达基因（DEGs），并探讨海马谷氨酸能突触改变在七氟醚诱导的老年小鼠认知功能障碍中的作用：我们采用单核RNA测序（snRNA-seq）技术研究了七氟烷诱导的老年小鼠海马兴奋性神经元的改变。对兴奋性神经元的基因本体（GO）和京都基因组百科全书（KEGG）进行了DEGs分析。最后，免疫荧光染色验证了七氟烷诱导的老龄小鼠海马谷氨酸能突触的交替：结果：这项研究表明，兴奋性神经元中的 DEGs 与谷氨酸能突触的减少和认知功能障碍有关。经过免疫荧光染色验证，我们还证实七氟醚麻醉降低了老年小鼠海马中谷氨酸能突触的密度：我们的研究结果表明，海马谷氨酸能突触的改变在七氟醚诱导的老年小鼠认知功能障碍中起着关键作用。

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.