• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

M2 皮质-背外侧纹状体刺激可逆转亨廷顿病的运动症状和突触缺陷。

M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington's disease.

机构信息

Departament de Biomedicina, Institut de Neurociències, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

出版信息

Elife. 2020 Oct 5;9:e57017. doi: 10.7554/eLife.57017.

DOI:10.7554/eLife.57017
PMID:33016873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7535932/
Abstract

Huntington's disease (HD) is a neurological disorder characterized by motor disturbances. HD pathology is most prominent in the striatum, the central hub of the basal ganglia. The cerebral cortex is the main striatal afferent, and progressive cortico-striatal disconnection characterizes HD. We mapped striatal network dysfunction in HD mice to ultimately modulate the activity of a specific cortico-striatal circuit to ameliorate motor symptoms and recover synaptic plasticity. Multimodal MRI in vivo indicates cortico-striatal and thalamo-striatal functional network deficits and reduced glutamate/glutamine ratio in the striatum of HD mice. Moreover, optogenetically-induced glutamate release from M2 cortex terminals in the dorsolateral striatum (DLS) was undetectable in HD mice and striatal neurons show blunted electrophysiological responses. Remarkably, repeated M2-DLS optogenetic stimulation normalized motor behavior in HD mice and evoked a sustained increase of synaptic plasticity. Overall, these results reveal that selective stimulation of the M2-DLS pathway can become an effective therapeutic strategy in HD.

摘要

亨廷顿病（HD）是一种以运动障碍为特征的神经退行性疾病。HD 病理学在纹状体中最为明显，纹状体是基底神经节的中枢枢纽。大脑皮层是纹状体的主要传入，进行性皮质纹状体分离是 HD 的特征。我们将 HD 小鼠的纹状体网络功能障碍进行映射，最终调节特定的皮质纹状体回路的活动，以改善运动症状并恢复突触可塑性。体内多模态 MRI 表明 HD 小鼠存在皮质纹状体和丘脑纹状体功能网络缺陷，以及纹状体中谷氨酸/谷氨酰胺比值降低。此外，在 HD 小鼠中，背外侧纹状体（DLS）中 M2 皮层末梢的光遗传学诱导谷氨酸释放无法检测到，并且纹状体神经元表现出电生理反应迟钝。值得注意的是，重复 M2-DLS 光遗传学刺激可使 HD 小鼠的运动行为正常化，并引起突触可塑性的持续增加。总的来说，这些结果表明，选择性刺激 M2-DLS 通路可能成为 HD 的一种有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/ac36d8a23ccc/elife-57017-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/e1718b149e84/elife-57017-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/383eb1cfa4be/elife-57017-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/9b4ac351b396/elife-57017-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/2eefe71a6678/elife-57017-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/1776ffd857cd/elife-57017-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/e775f0b9079c/elife-57017-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/790370b15bad/elife-57017-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/c260543f5e66/elife-57017-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/48fff6832b87/elife-57017-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/25850a36b7aa/elife-57017-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/ac36d8a23ccc/elife-57017-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/e1718b149e84/elife-57017-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/383eb1cfa4be/elife-57017-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/9b4ac351b396/elife-57017-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/2eefe71a6678/elife-57017-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/1776ffd857cd/elife-57017-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/e775f0b9079c/elife-57017-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/790370b15bad/elife-57017-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/c260543f5e66/elife-57017-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/48fff6832b87/elife-57017-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/25850a36b7aa/elife-57017-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2063/7535932/ac36d8a23ccc/elife-57017-fig6-figsupp1.jpg

相似文献

1
M2 cortex-dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington's disease.M2 皮质-背外侧纹状体刺激可逆转亨廷顿病的运动症状和突触缺陷。
Elife. 2020 Oct 5;9:e57017. doi: 10.7554/eLife.57017.
2
Striatal Direct and Indirect Pathway Output Structures Are Differentially Altered in Mouse Models of Huntington's Disease.纹状体直接和间接通路输出结构在亨廷顿病小鼠模型中发生差异改变。
J Neurosci. 2018 May 16;38(20):4678-4694. doi: 10.1523/JNEUROSCI.0434-18.2018. Epub 2018 Apr 24.
3
M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus.亨廷顿病中 M2 皮层回路和感觉诱导的行为改变：上丘的作用。
J Neurosci. 2023 May 3;43(18):3379-3390. doi: 10.1523/JNEUROSCI.1172-22.2023. Epub 2023 Mar 31.
4
Endocannabinoid-Specific Impairment in Synaptic Plasticity in Striatum of Huntington's Disease Mouse Model.亨廷顿病小鼠模型纹状体中内源性大麻素系统特异性突触可塑性障碍。
J Neurosci. 2018 Jan 17;38(3):544-554. doi: 10.1523/JNEUROSCI.1739-17.2017. Epub 2017 Nov 30.
5
Deficits in coordinated neuronal activity and network topology are striatal hallmarks in Huntington's disease.协调神经元活动和网络拓扑的缺陷是亨廷顿病的纹状体特征。
BMC Biol. 2020 May 28;18(1):58. doi: 10.1186/s12915-020-00794-4.
6
Direct assessment of presynaptic modulation of cortico-striatal glutamate release in a Huntington's disease mouse model.亨廷顿舞蹈病小鼠模型中皮质-纹状体谷氨酸释放的突触前调制的直接评估
J Neurophysiol. 2018 Dec 1;120(6):3077-3084. doi: 10.1152/jn.00638.2018. Epub 2018 Oct 17.
7
Deficit in Motor Skill Consolidation-Dependent Synaptic Plasticity at Motor Cortex to Dorsolateral Striatum Synapses in a Mouse Model of Huntington's Disease.亨廷顿病小鼠模型中运动皮层到背外侧纹状体突触的运动技能巩固相关突触可塑性缺陷。
eNeuro. 2020 Apr 7;7(2). doi: 10.1523/ENEURO.0297-19.2020. Print 2020 Mar/Apr.
8
Astrocyte Signaling Gates Long-Term Depression at Corticostriatal Synapses of the Direct Pathway.星形胶质细胞信号调控直接通路皮质纹状体突触的长时程抑制。
J Neurosci. 2020 Jul 22;40(30):5757-5768. doi: 10.1523/JNEUROSCI.2369-19.2020. Epub 2020 Jun 15.
9
Inactivation of adenosine A2A receptors reverses working memory deficits at early stages of Huntington's disease models.在亨廷顿病模型的早期阶段，腺苷 A2A 受体的失活可逆转工作记忆缺陷。
Neurobiol Dis. 2015 Jul;79:70-80. doi: 10.1016/j.nbd.2015.03.030. Epub 2015 Apr 16.
10
Differential impact of optogenetic stimulation of direct and indirect pathways from dorsolateral and dorsomedial striatum on motor symptoms in Huntington's disease mice.背外侧和背内侧纹状体直接和间接通路的光遗传刺激对亨廷顿病小鼠运动症状的影响差异。
Exp Neurol. 2025 Jan;383:114991. doi: 10.1016/j.expneurol.2024.114991. Epub 2024 Oct 9.

引用本文的文献

1
Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review.基于网络药理学方法解析天然产物的神经保护潜力：一篇综述
Mol Divers. 2025 Apr 25. doi: 10.1007/s11030-025-11198-3.
2
Presymptomatic targeted circuit manipulation for ameliorating Huntington's disease pathogenesis.用于改善亨廷顿病发病机制的症状前靶向回路操纵。
iScience. 2025 Feb 13;28(3):112022. doi: 10.1016/j.isci.2025.112022. eCollection 2025 Mar 21.
3
Optogenetic restoration of neuron subtype-specific cortical activity ameliorates motor deficits in Huntington's Disease mice.

本文引用的文献

1
Corticostriatal synaptic plasticity alterations in the R6/1 transgenic mouse model of Huntington's disease.亨廷顿病 R6/1 转基因小鼠模型中海马体-纹状体突触可塑性的改变。
J Neurosci Res. 2019 Dec;97(12):1655-1664. doi: 10.1002/jnr.24521. Epub 2019 Sep 9.
2
Increased translation as a novel pathogenic mechanism in Huntington's disease.翻译增强是亨廷顿病的一种新发病机制。
Brain. 2019 Oct 1;142(10):3158-3175. doi: 10.1093/brain/awz230.
3
Cortical circuit alterations precede motor impairments in Huntington's disease mice.皮质电路改变先于亨廷顿病小鼠的运动障碍。
光遗传学恢复神经元亚型特异性皮层活动可改善亨廷顿舞蹈症小鼠的运动缺陷。
bioRxiv. 2025 Feb 8:2025.02.07.637155. doi: 10.1101/2025.02.07.637155.
4
Advancing Neuroscience and Therapy: Insights into Genetic and Non-Genetic Neuromodulation Approaches.推进神经科学与治疗：对基因和非基因神经调节方法的见解。
Cells. 2025 Jan 15;14(2):122. doi: 10.3390/cells14020122.
5
Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum.敲除 TAAR5：纹状体中增强神经发生和多巴胺信号传导的一种途径。
Cells. 2024 Nov 19;13(22):1910. doi: 10.3390/cells13221910.
6
Presymptomatic Targeted Circuit Manipulation for Ameliorating Huntington's Disease Pathogenesis.用于改善亨廷顿病发病机制的症状前靶向神经回路操控
bioRxiv. 2024 Jul 24:2024.07.24.604946. doi: 10.1101/2024.07.24.604946.
7
Application of Optogenetics in Neurodegenerative Diseases.光遗传学在神经退行性疾病中的应用。
Cell Mol Neurobiol. 2024 Jul 26;44(1):57. doi: 10.1007/s10571-024-01486-1.
8
Preserved VPS13A distribution and expression in Huntington's disease: divergent mechanisms of action for similar movement disorders?亨廷顿舞蹈病中VPS13A分布及表达的保留：相似运动障碍的不同作用机制？
Front Neurosci. 2024 Jun 5;18:1394478. doi: 10.3389/fnins.2024.1394478. eCollection 2024.
9
Motor skill learning modulates striatal extracellular vesicles' content in a mouse model of Huntington's disease.运动技能学习可调节亨廷顿病小鼠模型纹状体细胞外囊泡的内容物。
Cell Commun Signal. 2024 Jun 11;22(1):321. doi: 10.1186/s12964-024-01693-9.
10
Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington's disease.亨廷顿病 zQ175DN 小鼠模型中脑灌注和血管反应性的纵向变化。
J Biomed Sci. 2024 Apr 16;31(1):37. doi: 10.1186/s12929-024-01028-3.
Sci Rep. 2019 Apr 29;9(1):6634. doi: 10.1038/s41598-019-43024-w.
4
Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson's Disease.光遗传学刺激 M2 皮层可逆转帕金森病小鼠模型的运动功能障碍。
J Neurosci. 2019 Apr 24;39(17):3234-3248. doi: 10.1523/JNEUROSCI.2277-18.2019. Epub 2019 Feb 19.
5
Disrupted striatal neuron inputs and outputs in Huntington's disease.亨廷顿病中纹状体神经元输入和输出的紊乱。
CNS Neurosci Ther. 2018 Apr;24(4):250-280. doi: 10.1111/cns.12844.
6
In vivo GluCEST MRI: Reproducibility, background contribution and source of glutamate changes in the MPTP model of Parkinson's disease.体内 GluCEST MRI：MPTP 帕金森病模型中谷氨酸变化的可重复性、背景贡献和来源。
Sci Rep. 2018 Feb 13;8(1):2883. doi: 10.1038/s41598-018-21035-3.
7
Integrated anatomical and physiological mapping of striatal afferent projections.纹状体传入投射的综合解剖和生理图谱。
Eur J Neurosci. 2019 Mar;49(5):623-636. doi: 10.1111/ejn.13829. Epub 2018 Feb 22.
8
Cdk5 Contributes to Huntington's Disease Learning and Memory Deficits via Modulation of Brain Region-Specific Substrates.Cdk5 通过调节大脑区域特异性底物对亨廷顿病的学习和记忆缺陷有贡献。
Mol Neurobiol. 2018 Aug;55(8):6250-6268. doi: 10.1007/s12035-017-0828-4. Epub 2017 Dec 29.
9
Molecular insights into cortico-striatal miscommunications in Huntington's disease.亨廷顿病中海马-纹状体通讯障碍的分子机制研究
Curr Opin Neurobiol. 2018 Feb;48:79-89. doi: 10.1016/j.conb.2017.10.019. Epub 2017 Nov 7.
10
Differential electrophysiological and morphological alterations of thalamostriatal and corticostriatal projections in the R6/2 mouse model of Huntington's disease.亨廷顿病 R6/2 小鼠模型中海马体-纹状体和皮质纹状体投射的电生理学和形态学差异改变。
Neurobiol Dis. 2017 Dec;108:29-44. doi: 10.1016/j.nbd.2017.07.020. Epub 2017 Jul 27.