靶向NEK7调节焦亡和肠道微生物群以减轻大鼠的抑郁样行为

IF 4.7 2区 医学 Q2 IMMUNOLOGY
Wenxuan Lang , Chongji Wang , Jiahui Wen , Miaoqi Chen , Decheng Wei , Yanzong Jiang , Xue Li , Pengsheng Wei , Ge Jin , Qiwen Zhu
{"title":"靶向NEK7调节焦亡和肠道微生物群以减轻大鼠的抑郁样行为","authors":"Wenxuan Lang ,&nbsp;Chongji Wang ,&nbsp;Jiahui Wen ,&nbsp;Miaoqi Chen ,&nbsp;Decheng Wei ,&nbsp;Yanzong Jiang ,&nbsp;Xue Li ,&nbsp;Pengsheng Wei ,&nbsp;Ge Jin ,&nbsp;Qiwen Zhu","doi":"10.1016/j.intimp.2025.115148","DOIUrl":null,"url":null,"abstract":"<div><div>NIMA-associated kinase 7 (NEK7) is a serine/threonine kinase that regulates the aberrant activation of the inflammasome of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), which leads to inflammatory diseases. Depression, a prevalent psychiatric condition, has been linked to neuroinflammatory processes. However, the precise molecular and cellular mechanisms underlying the role of NEK7 in depression pathogenesis remain incompletely characterized. Our study demonstrated elevated NEK7 expression in the hippocampus of maternal separation (MS) and chronic unpredictable mild stress (CUMS)-induced depressed rats. Adeno-associated virus (AAV)-mediated delivery of shNEK7 effectively alleviated depression-like behavioral deficits, downregulated pyroptosis marker protein expression, reduced inflammatory cytokine levels (interleukin-1β and interleukin-18), and preserved neuronal survival and cellular structure. Furthermore, hippocampal NEK7 knockdown restored gut microbiota homeostasis in depression-like rats, particularly affecting the relative abundance of <em>Corynebacterium</em> and <em>Prevotella</em> genera. Notably, for the first time, the metabolite corynoxine was found to be associated with hippocampal NEK7 knockdown in depression-like rats. Taken together, our results reveal that NEK7 may be a promising target for the treatment of depression and provide new experimental evidence for clinical application.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"162 ","pages":"Article 115148"},"PeriodicalIF":4.7000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeting NEK7 modulates pyroptosis and gut microbiota to alleviate depression-like behavior in rats\",\"authors\":\"Wenxuan Lang ,&nbsp;Chongji Wang ,&nbsp;Jiahui Wen ,&nbsp;Miaoqi Chen ,&nbsp;Decheng Wei ,&nbsp;Yanzong Jiang ,&nbsp;Xue Li ,&nbsp;Pengsheng Wei ,&nbsp;Ge Jin ,&nbsp;Qiwen Zhu\",\"doi\":\"10.1016/j.intimp.2025.115148\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>NIMA-associated kinase 7 (NEK7) is a serine/threonine kinase that regulates the aberrant activation of the inflammasome of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), which leads to inflammatory diseases. Depression, a prevalent psychiatric condition, has been linked to neuroinflammatory processes. However, the precise molecular and cellular mechanisms underlying the role of NEK7 in depression pathogenesis remain incompletely characterized. Our study demonstrated elevated NEK7 expression in the hippocampus of maternal separation (MS) and chronic unpredictable mild stress (CUMS)-induced depressed rats. Adeno-associated virus (AAV)-mediated delivery of shNEK7 effectively alleviated depression-like behavioral deficits, downregulated pyroptosis marker protein expression, reduced inflammatory cytokine levels (interleukin-1β and interleukin-18), and preserved neuronal survival and cellular structure. Furthermore, hippocampal NEK7 knockdown restored gut microbiota homeostasis in depression-like rats, particularly affecting the relative abundance of <em>Corynebacterium</em> and <em>Prevotella</em> genera. Notably, for the first time, the metabolite corynoxine was found to be associated with hippocampal NEK7 knockdown in depression-like rats. Taken together, our results reveal that NEK7 may be a promising target for the treatment of depression and provide new experimental evidence for clinical application.</div></div>\",\"PeriodicalId\":13859,\"journal\":{\"name\":\"International immunopharmacology\",\"volume\":\"162 \",\"pages\":\"Article 115148\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International immunopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1567576925011385\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925011385","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

nima相关激酶7 (NEK7)是一种丝氨酸/苏氨酸激酶,可调节nod样受体热蛋白结构域相关蛋白3 (NLRP3)炎症小体的异常激活,从而导致炎症性疾病。抑郁症是一种普遍的精神疾病,与神经炎症过程有关。然而,NEK7在抑郁症发病机制中的精确分子和细胞机制仍未完全确定。我们的研究表明,母性分离(MS)和慢性不可预测轻度应激(CUMS)诱导的抑郁症大鼠海马中NEK7表达升高。腺相关病毒(AAV)介导的递送shNEK7有效缓解抑郁样行为缺陷,下调焦亡标志物蛋白表达,降低炎症细胞因子(白细胞介素-1β和白细胞介素-18)水平,保存神经元存活和细胞结构。此外,海马NEK7敲低恢复了抑郁样大鼠肠道微生物群的稳态,特别是影响了棒状杆菌和普雷沃氏菌属的相对丰度。值得注意的是,首次发现代谢物氯草胺与抑郁样大鼠海马NEK7敲低有关。综上所述,我们的研究结果表明NEK7可能是治疗抑郁症的一个有希望的靶点,为临床应用提供了新的实验证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Targeting NEK7 modulates pyroptosis and gut microbiota to alleviate depression-like behavior in rats

Targeting NEK7 modulates pyroptosis and gut microbiota to alleviate depression-like behavior in rats
NIMA-associated kinase 7 (NEK7) is a serine/threonine kinase that regulates the aberrant activation of the inflammasome of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), which leads to inflammatory diseases. Depression, a prevalent psychiatric condition, has been linked to neuroinflammatory processes. However, the precise molecular and cellular mechanisms underlying the role of NEK7 in depression pathogenesis remain incompletely characterized. Our study demonstrated elevated NEK7 expression in the hippocampus of maternal separation (MS) and chronic unpredictable mild stress (CUMS)-induced depressed rats. Adeno-associated virus (AAV)-mediated delivery of shNEK7 effectively alleviated depression-like behavioral deficits, downregulated pyroptosis marker protein expression, reduced inflammatory cytokine levels (interleukin-1β and interleukin-18), and preserved neuronal survival and cellular structure. Furthermore, hippocampal NEK7 knockdown restored gut microbiota homeostasis in depression-like rats, particularly affecting the relative abundance of Corynebacterium and Prevotella genera. Notably, for the first time, the metabolite corynoxine was found to be associated with hippocampal NEK7 knockdown in depression-like rats. Taken together, our results reveal that NEK7 may be a promising target for the treatment of depression and provide new experimental evidence for clinical application.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信