Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice.

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2024-11-27 eCollection Date: 2024-11-01 DOI:10.1371/journal.pbio.3002888
Fang Tong, Shuai Liu, Chen Zhang, Xicheng Gu, Huan Yang, Bin Zhou, Yun-Yun Wang, Jianwei Chen, Qianhui Qu, Ye Gong, Haili Pan, Chen Liang, Changlin Li, Xin Zhang, Qingjian Han
{"title":"Elevated vesicular Zn2+ in dorsal root ganglion neurons expressing the transporter TMEM163 causes age-associated itchy skin in mice.","authors":"Fang Tong, Shuai Liu, Chen Zhang, Xicheng Gu, Huan Yang, Bin Zhou, Yun-Yun Wang, Jianwei Chen, Qianhui Qu, Ye Gong, Haili Pan, Chen Liang, Changlin Li, Xin Zhang, Qingjian Han","doi":"10.1371/journal.pbio.3002888","DOIUrl":null,"url":null,"abstract":"<p><p>The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163. These neurons form direct synapses with and modulate the activity of spinal NPY+ inhibitory interneurons. In aged mice, both the expression of TMEM163 and the concentration of vesicular Zn2+ within the central terminals of TMEM163+ primary afferents show marked elevation. Importantly, the excessive release of vesicular Zn2+ significantly dampens the activity of NPY+ neurons, triggering the disinhibition of itch-transmitting neural circuits and resulting in chronic itch. Intriguingly, chelating Zn2+ within the spinal dorsal horn effectively relieves itch in aged mice. Our study thus unveils a novel molecular mechanism underlying senile pruritus.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 11","pages":"e3002888"},"PeriodicalIF":9.8000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602076/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pbio.3002888","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Agricultural and Biological Sciences","Score":null,"Total":0}
引用次数: 0

Abstract

The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163. These neurons form direct synapses with and modulate the activity of spinal NPY+ inhibitory interneurons. In aged mice, both the expression of TMEM163 and the concentration of vesicular Zn2+ within the central terminals of TMEM163+ primary afferents show marked elevation. Importantly, the excessive release of vesicular Zn2+ significantly dampens the activity of NPY+ neurons, triggering the disinhibition of itch-transmitting neural circuits and resulting in chronic itch. Intriguingly, chelating Zn2+ within the spinal dorsal horn effectively relieves itch in aged mice. Our study thus unveils a novel molecular mechanism underlying senile pruritus.

表达转运体 TMEM163 的背根神经节神经元中的囊泡 Zn2+ 升高会导致小鼠出现年龄相关性皮肤瘙痒。
与衰老相关的普遍瘙痒症历来被称为老年性瘙痒症,它降低了人们的生活质量。尽管瘙痒症影响很大,但有效的治疗方法仍然难以捉摸,这主要是由于对其病理原因了解不全面。在这项研究中,我们发现了一个富含 Zn2+ 的背根神经节神经元亚群,它们表达囊状 Zn2+ 转运体 TMEM163。这些神经元与脊髓NPY+抑制性中间神经元形成直接突触并调节其活动。在老龄小鼠中,TMEM163 的表达和 TMEM163+ 初级传入神经元中央末梢内的囊泡 Zn2+ 浓度都明显升高。重要的是,囊泡 Zn2+ 的过度释放会显著抑制 NPY+ 神经元的活性,引发痒传导神经回路的抑制失调,导致慢性瘙痒。有趣的是,在脊髓背角内螯合 Zn2+ 能有效缓解老年小鼠的瘙痒。因此,我们的研究揭示了老年性瘙痒症的一种新的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
×
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:481959085
Book学术官方微信