CISD2通过抑制铁下垂和维持小鼠海马神经元的树突棘密度来改善中暑相关的早期认知缺陷。

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Liang Zeng , Jinhan Sun , Kai Ji , Lianxiang Zhang , Jiandong Niu , Kang Ma , Yan Yan , Zhiping Hei , Yuning Sun
{"title":"CISD2通过抑制铁下垂和维持小鼠海马神经元的树突棘密度来改善中暑相关的早期认知缺陷。","authors":"Liang Zeng ,&nbsp;Jinhan Sun ,&nbsp;Kai Ji ,&nbsp;Lianxiang Zhang ,&nbsp;Jiandong Niu ,&nbsp;Kang Ma ,&nbsp;Yan Yan ,&nbsp;Zhiping Hei ,&nbsp;Yuning Sun","doi":"10.1016/j.neuroscience.2025.05.024","DOIUrl":null,"url":null,"abstract":"<div><div>Heatstroke encephalopathy is a universal primary manifestation of heatstroke. Early brain injury caused by heatstroke may lead to long-term cognitive impairment in survivors, yet it frequently evades detection by standard diagnostic techniques. Thus, the discovery of reliable biomarkers for early brain injury detection is necessary. In this study, CISD2 downregulation in HT-22 cells was observed following hyperthermia treatment by using transcriptomics analysis. Subsequent mechanistic investigations revealed that CISD2 downregulation triggeres ferroptosis via AMPK-dependent BECN1 phosphorylation at Ser93, while CISD2 overexpression confers ferroptosis resistance in HT-22 cells at 41 °C. Furthermore, the downregulation of CISD2 expression and ferroptotic alterations were firmly observed in hippocampal tissues of mice during the early stage of heatstroke, and the overexpression of CISD2 by injecting lentivirus overexpressing CISD2 into the hippocampus of mice significantly alleviated heatstroke-induced neuronal loss, and meanwhile, the density of dendritic spines in the CA1 pyramidal neurons of the mice was effectively preserved. Moreover, knockdown of the CISD2 in the hippocampus exacerbated the loss of hippocampal neurons and the reduction of dendritic spine density. In summary, our results illustrated that CISD2 plays a pivotal role in preserving normal hippocampal function by regulating lipid peroxidation and iron homeostasis of heatstroke conditions. These finds provide novel insights into the mechanisms underlying heatstroke-induced cognitive deficits and offer potential strategies for improving risk prediction of heatstroke encephalopathy.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"577 ","pages":"Pages 282-299"},"PeriodicalIF":2.8000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CISD2 ameliorates heatstroke-associated early cognitive deficits by inhibiting ferroptosis and maintaining dendritic spine density in hippocampal neurons in mice\",\"authors\":\"Liang Zeng ,&nbsp;Jinhan Sun ,&nbsp;Kai Ji ,&nbsp;Lianxiang Zhang ,&nbsp;Jiandong Niu ,&nbsp;Kang Ma ,&nbsp;Yan Yan ,&nbsp;Zhiping Hei ,&nbsp;Yuning Sun\",\"doi\":\"10.1016/j.neuroscience.2025.05.024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Heatstroke encephalopathy is a universal primary manifestation of heatstroke. Early brain injury caused by heatstroke may lead to long-term cognitive impairment in survivors, yet it frequently evades detection by standard diagnostic techniques. Thus, the discovery of reliable biomarkers for early brain injury detection is necessary. In this study, CISD2 downregulation in HT-22 cells was observed following hyperthermia treatment by using transcriptomics analysis. Subsequent mechanistic investigations revealed that CISD2 downregulation triggeres ferroptosis via AMPK-dependent BECN1 phosphorylation at Ser93, while CISD2 overexpression confers ferroptosis resistance in HT-22 cells at 41 °C. Furthermore, the downregulation of CISD2 expression and ferroptotic alterations were firmly observed in hippocampal tissues of mice during the early stage of heatstroke, and the overexpression of CISD2 by injecting lentivirus overexpressing CISD2 into the hippocampus of mice significantly alleviated heatstroke-induced neuronal loss, and meanwhile, the density of dendritic spines in the CA1 pyramidal neurons of the mice was effectively preserved. Moreover, knockdown of the CISD2 in the hippocampus exacerbated the loss of hippocampal neurons and the reduction of dendritic spine density. In summary, our results illustrated that CISD2 plays a pivotal role in preserving normal hippocampal function by regulating lipid peroxidation and iron homeostasis of heatstroke conditions. These finds provide novel insights into the mechanisms underlying heatstroke-induced cognitive deficits and offer potential strategies for improving risk prediction of heatstroke encephalopathy.</div></div>\",\"PeriodicalId\":19142,\"journal\":{\"name\":\"Neuroscience\",\"volume\":\"577 \",\"pages\":\"Pages 282-299\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0306452225003860\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0306452225003860","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

中暑脑病是中暑常见的主要表现。中暑引起的早期脑损伤可能导致幸存者长期认知障碍,但标准诊断技术往往无法检测到。因此,发现可靠的早期脑损伤检测生物标志物是必要的。在本研究中,通过转录组学分析观察到高温治疗后HT-22细胞中CISD2的下调。随后的机制研究表明,CISD2下调通过ampk依赖性BECN1 Ser93磷酸化触发铁死亡,而CISD2过表达在41 °C时赋予HT-22细胞铁死亡抗性。此外,在中暑早期小鼠海马组织中可以明显观察到CISD2表达下调和铁致改变,通过向小鼠海马中注射过表达CISD2的慢病毒来过表达CISD2,可以显著减轻中暑诱导的神经元丢失,同时有效地保留小鼠CA1锥体神经元的树突棘密度。此外,海马中CISD2的敲低加剧了海马神经元的丢失和树突棘密度的降低。综上所述,我们的研究结果表明,CISD2通过调节中暑条件下的脂质过氧化和铁稳态,在维持正常海马功能中起关键作用。这些发现为中暑导致的认知缺陷的潜在机制提供了新的见解,并为改进中暑脑病的风险预测提供了潜在的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

CISD2 ameliorates heatstroke-associated early cognitive deficits by inhibiting ferroptosis and maintaining dendritic spine density in hippocampal neurons in mice

CISD2 ameliorates heatstroke-associated early cognitive deficits by inhibiting ferroptosis and maintaining dendritic spine density in hippocampal neurons in mice
Heatstroke encephalopathy is a universal primary manifestation of heatstroke. Early brain injury caused by heatstroke may lead to long-term cognitive impairment in survivors, yet it frequently evades detection by standard diagnostic techniques. Thus, the discovery of reliable biomarkers for early brain injury detection is necessary. In this study, CISD2 downregulation in HT-22 cells was observed following hyperthermia treatment by using transcriptomics analysis. Subsequent mechanistic investigations revealed that CISD2 downregulation triggeres ferroptosis via AMPK-dependent BECN1 phosphorylation at Ser93, while CISD2 overexpression confers ferroptosis resistance in HT-22 cells at 41 °C. Furthermore, the downregulation of CISD2 expression and ferroptotic alterations were firmly observed in hippocampal tissues of mice during the early stage of heatstroke, and the overexpression of CISD2 by injecting lentivirus overexpressing CISD2 into the hippocampus of mice significantly alleviated heatstroke-induced neuronal loss, and meanwhile, the density of dendritic spines in the CA1 pyramidal neurons of the mice was effectively preserved. Moreover, knockdown of the CISD2 in the hippocampus exacerbated the loss of hippocampal neurons and the reduction of dendritic spine density. In summary, our results illustrated that CISD2 plays a pivotal role in preserving normal hippocampal function by regulating lipid peroxidation and iron homeostasis of heatstroke conditions. These finds provide novel insights into the mechanisms underlying heatstroke-induced cognitive deficits and offer potential strategies for improving risk prediction of heatstroke encephalopathy.
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
Neuroscience
Neuroscience 医学-神经科学
CiteScore
6.20
自引率
0.00%
发文量
394
审稿时长
52 days
期刊介绍: Neuroscience publishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.
×
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