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氯胺酮诱导大鼠肠道微生物群失调以及肠道屏障和海马功能障碍。

Ketamine induced gut microbiota dysbiosis and barrier and hippocampal dysfunction in rats.

作者信息

Xie Lei, Zhuang Zelin, Guo Baowen, Huang Yuehua, Shi Xiaoyan, Huang Zikai, Xu Ziquan, Chen Yanbin, Cao Yuyin, Zheng Yanmin, Wu Renhua, Ma Shuhua

机构信息

Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.

Laboratory of Molecular Imaging & Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.

出版信息

iScience. 2024 Sep 30;27(11):111089. doi: 10.1016/j.isci.2024.111089. eCollection 2024 Nov 15.

DOI:10.1016/j.isci.2024.111089
PMID:39493883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11530865/
Abstract

The microbiota-gut-brain axis (MGBA) plays a pivotal role in drug addiction. However, the pathophysiological mechanism of MGBA in ketamine addiction remains elusive. The present study investigated the ketamine-induced gut microbiota disorders, intestinal barrier dysfunction, and the alterations in brain function, using a conditioned place preference (CPP) model of ketamine addiction in rats. Compared with the control group, ketamine induced decreased amplitude of low-frequency fluctuation (ALFF) values in the hippocampus, and pyknotic nuclei and concentrated cytoplasm in hippocampal neurons, as well as alterations in gut microbiota composition, shortened ileum villi, and thinner colonic mucosa. We also found that the abundance of gut microbiota exhibited correlations with CPP score, hippocampal ALFF value, length of ileum villi, and thickness of colonic mucosa. Our findings provide evidence for abnormal alterations in the MGBA of ketamine-addicted rats, which improves our understating of the mechanism of ketamine addiction and the potential for developing new therapeutic strategies.

摘要

微生物群-肠道-脑轴（MGBA）在药物成瘾中起关键作用。然而，MGBA在氯胺酮成瘾中的病理生理机制仍不清楚。本研究使用大鼠氯胺酮成瘾的条件性位置偏爱（CPP）模型，研究了氯胺酮诱导的肠道微生物群紊乱、肠道屏障功能障碍以及脑功能变化。与对照组相比，氯胺酮导致海马区低频振幅（ALFF）值降低，海马神经元细胞核固缩、细胞质浓缩，以及肠道微生物群组成改变、回肠绒毛缩短和结肠黏膜变薄。我们还发现肠道微生物群的丰度与CPP评分、海马ALFF值、回肠绒毛长度和结肠黏膜厚度相关。我们的研究结果为氯胺酮成瘾大鼠MGBA的异常改变提供了证据，这有助于我们更好地理解氯胺酮成瘾的机制以及开发新治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/28e873ac647d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/13b3e71b3ada/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/ea96308d6cd3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/60d2b0bdeae9/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/6dfb13e0ab44/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/3e53ab32cc8d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/1369f15f0903/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/28e873ac647d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/13b3e71b3ada/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/ea96308d6cd3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/60d2b0bdeae9/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/6dfb13e0ab44/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/3e53ab32cc8d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/1369f15f0903/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf78/11530865/28e873ac647d/gr6.jpg

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本文引用的文献

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Metab Brain Dis. 2023 Oct;38(7):2417-2426. doi: 10.1007/s11011-023-01236-0. Epub 2023 Jun 5.
2
The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence.海洛因依赖小鼠肠道微生物群改变与肠道黏膜屏障完整性的关联
Front Nutr. 2021 Nov 4;8:765414. doi: 10.3389/fnut.2021.765414. eCollection 2021.
3
The upregulation of Nur77 decreases ketamine-induced hippocampal neurons toxicity in rats.
Nur77 的上调可降低氯胺酮诱导的大鼠海马神经元毒性。
Neuroreport. 2021 Dec 8;32(17):1370-1378. doi: 10.1097/WNR.0000000000001738.
4
Roles of Gut Microbiota in the Regulation of Hippocampal Plasticity, Inflammation, and Hippocampus-Dependent Behaviors.肠道微生物群在调节海马体可塑性、炎症和海马体依赖行为中的作用。
Front Cell Infect Microbiol. 2021 Jan 27;10:611014. doi: 10.3389/fcimb.2020.611014. eCollection 2020.
5
Opioid agonist and antagonist use and the gut microbiota: associations among people in addiction treatment.阿片类激动剂和拮抗剂的使用与肠道微生物群：接受成瘾治疗人群中的关联。
Sci Rep. 2020 Nov 10;10(1):19471. doi: 10.1038/s41598-020-76570-9.
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Microbiome and substances of abuse.微生物组与滥用物质。
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110113. doi: 10.1016/j.pnpbp.2020.110113. Epub 2020 Sep 22.
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maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa.维持肠道上皮再生并修复受损的肠黏膜。
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Current Perspectives on Gut Microbiome Dysbiosis and Depression.肠道微生物组失调与抑郁症的研究现状。
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