脑特异性牛磺酸病损害外周骨骼肌的完整性和功能

IF 1.7 Q3 CLINICAL NEUROLOGY Aging brain Pub Date : 2024-01-01 DOI:10.1016/j.nbas.2024.100110
Bryan Alava , Gabriela Hery , Silvana Sidhom , Miguel Gutierrez-Monreal , Stefan Prokop , Karyn A. Esser , Jose Abisambra
{"title":"脑特异性牛磺酸病损害外周骨骼肌的完整性和功能","authors":"Bryan Alava ,&nbsp;Gabriela Hery ,&nbsp;Silvana Sidhom ,&nbsp;Miguel Gutierrez-Monreal ,&nbsp;Stefan Prokop ,&nbsp;Karyn A. Esser ,&nbsp;Jose Abisambra","doi":"10.1016/j.nbas.2024.100110","DOIUrl":null,"url":null,"abstract":"<div><p>Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8). AAV8-P301L mice showed grip strength deficits, hyperactivity, and abnormal histological features of skeletal muscle. Additionally, spatially resolved gene expression of muscle cross sections were altered in AAV8-P301L myofibers. Transcriptional changes showed alterations of genes encoding sarcomeric proteins, proposing a weakness phenotype. Strikingly, specific force of the soleus muscle was blunted in AAV8-P301L tau male mice. Our findings suggest tauopathy has peripheral consequences in skeletal muscle that contribute to weakness in tauopathy.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589958924000057/pdfft?md5=9013d5b5fc8f1c0ab274640c4767554a&pid=1-s2.0-S2589958924000057-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function\",\"authors\":\"Bryan Alava ,&nbsp;Gabriela Hery ,&nbsp;Silvana Sidhom ,&nbsp;Miguel Gutierrez-Monreal ,&nbsp;Stefan Prokop ,&nbsp;Karyn A. Esser ,&nbsp;Jose Abisambra\",\"doi\":\"10.1016/j.nbas.2024.100110\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8). AAV8-P301L mice showed grip strength deficits, hyperactivity, and abnormal histological features of skeletal muscle. Additionally, spatially resolved gene expression of muscle cross sections were altered in AAV8-P301L myofibers. Transcriptional changes showed alterations of genes encoding sarcomeric proteins, proposing a weakness phenotype. Strikingly, specific force of the soleus muscle was blunted in AAV8-P301L tau male mice. Our findings suggest tauopathy has peripheral consequences in skeletal muscle that contribute to weakness in tauopathy.</p></div>\",\"PeriodicalId\":72131,\"journal\":{\"name\":\"Aging brain\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2589958924000057/pdfft?md5=9013d5b5fc8f1c0ab274640c4767554a&pid=1-s2.0-S2589958924000057-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Aging brain\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2589958924000057\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging brain","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589958924000057","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

牛头蛋白病是一种神经退行性疾病,细胞内牛头蛋白的病理性聚集会导致认知障碍。此外,临床研究报告称,患有牛头蛋白病的人群肌肉无力。然而,神经元病理tau物种是否会导致肌肉无力,以及原发性tau病的骨骼肌是否能保持收缩能力,目前仍是未知数。在这里,我们利用腺相关病毒血清型8(AAV8)表达人类突变体P301L-tau,在原发性tau病小鼠模型中发现了骨骼肌异常。AAV8-P301L 小鼠表现出握力缺陷、多动和骨骼肌组织学特征异常。此外,AAV8-P301L肌纤维肌肉横截面的空间分辨基因表达也发生了改变。转录变化显示编码肌纤维蛋白的基因发生了改变,从而提出了一种虚弱表型。引人注目的是,AAV8-P301L tau雄性小鼠比目鱼肌的特异性力量减弱。我们的研究结果表明,tau病会对骨骼肌产生外周影响,从而导致tau病的虚弱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function

Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8). AAV8-P301L mice showed grip strength deficits, hyperactivity, and abnormal histological features of skeletal muscle. Additionally, spatially resolved gene expression of muscle cross sections were altered in AAV8-P301L myofibers. Transcriptional changes showed alterations of genes encoding sarcomeric proteins, proposing a weakness phenotype. Strikingly, specific force of the soleus muscle was blunted in AAV8-P301L tau male mice. Our findings suggest tauopathy has peripheral consequences in skeletal muscle that contribute to weakness in tauopathy.

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
Aging brain
Aging brain Neuroscience (General), Geriatrics and Gerontology
自引率
0.00%
发文量
0
期刊最新文献
Age-related differences in structural and resting-state functional brain network organization across the adult lifespan: A cross-sectional study Age-related fornix decline predicts conservative response strategy-based slowing in perceptual decision-making Age-related decline in social interaction is associated with decreased c-Fos induction in select brain regions independent of oxytocin receptor expression profiles Innate immunity in brain aging and neurodegeneration Neural correlates of home-based intervention effects on value-based sequential decision-making in healthy older adults
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1