星形胶质细胞与亨廷顿病。
Astrocytes and Huntington's disease.
机构信息
Departments of Physiology, ‡Neurobiology, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, California 90095-1751, United States.
出版信息
ACS Chem Neurosci. 2014 Jul 16;5(7):494-6. doi: 10.1021/cn500100r. Epub 2014 May 20.
Abstract
In this Viewpoint, we summarize and discuss the recent serendipitous discovery of an astrocyte Kir4.1 potassium channel dysfunction in two mouse models of Huntington's disease (HD). Restoration of Kir4.1 channels within astrocytes in vivo attenuated neuronal dysfunction, some aspects of motor dysfunction and increased survival time in a HD mouse model. Overall, the data show that aspects of altered neuronal excitability associated with HD may be secondary to changes in astrocyte-mediated K(+) homeostasis, thereby revealing a new striatal neural microcircuit mechanism in HD, and Kir4.1 channels and astrocytes as potential therapeutic targets for drug development.
摘要
在本观点中，我们总结并讨论了最近在两种亨廷顿病（HD）小鼠模型中偶然发现的星形胶质细胞 Kir4.1 钾通道功能障碍。在体内恢复星形胶质细胞中的 Kir4.1 通道可减弱神经元功能障碍、运动功能障碍的某些方面，并延长 HD 小鼠模型的存活时间。总体而言，这些数据表明与 HD 相关的神经元兴奋性改变的某些方面可能是星形胶质细胞介导的 K(+)稳态改变的结果，从而揭示了 HD 中的新纹状体神经微电路机制，以及 Kir4.1 通道和星形胶质细胞作为药物开发的潜在治疗靶点。
相似文献
1
Astrocytes and Huntington's disease.星形胶质细胞与亨廷顿病。
ACS Chem Neurosci. 2014 Jul 16;5(7):494-6. doi: 10.1021/cn500100r. Epub 2014 May 20.
2
Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice.星形胶质细胞 Kir4.1 离子通道缺陷导致亨廷顿病模型小鼠神经元功能障碍。
Nat Neurosci. 2014 May;17(5):694-703. doi: 10.1038/nn.3691. Epub 2014 Mar 30.
3
Dysfunctional Calcium and Glutamate Signaling in Striatal Astrocytes from Huntington's Disease Model Mice.亨廷顿舞蹈病模型小鼠纹状体星形胶质细胞中钙信号和谷氨酸信号功能失调
J Neurosci. 2016 Mar 23;36(12):3453-70. doi: 10.1523/JNEUROSCI.3693-15.2016.
4
Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease.揭示与利用亨廷顿舞蹈病中的星形胶质细胞功能障碍
Trends Neurosci. 2017 Jul;40(7):422-437. doi: 10.1016/j.tins.2017.05.002. Epub 2017 May 31.
5
Functional Indicators of Glutamate Transport in Single Striatal Astrocytes and the Influence of Kir4.1 in Normal and Huntington Mice.单纹状体星形胶质细胞中谷氨酸转运的功能指标以及Kir4.1在正常和亨廷顿病小鼠中的影响
J Neurosci. 2016 May 4;36(18):4959-75. doi: 10.1523/JNEUROSCI.0316-16.2016.
6
Systemic application of AAV vectors targeting GFAP-expressing astrocytes in Z-Q175-KI Huntington's disease mice.在Z-Q175-KI亨廷顿舞蹈病小鼠中对靶向表达胶质纤维酸性蛋白（GFAP）的星形胶质细胞的腺相关病毒（AAV）载体进行全身应用。
Mol Cell Neurosci. 2016 Dec;77:76-86. doi: 10.1016/j.mcn.2016.10.007. Epub 2016 Oct 27.
7
Neuronal vulnerability in mouse models of Huntington's disease: membrane channel protein changes.亨廷顿舞蹈症小鼠模型中的神经元易损性：膜通道蛋白变化
J Neurosci Res. 2005 Jun 1;80(5):634-45. doi: 10.1002/jnr.20492.
8
Emerging Roles of Astrocyte Kir4.1 Channels in the Pathogenesis and Treatment of Brain Diseases.星形胶质细胞 Kir4.1 通道在脑部疾病发病机制和治疗中的新作用。
Int J Mol Sci. 2021 Sep 23;22(19):10236. doi: 10.3390/ijms221910236.
9
Systems Genetic Analyses Highlight a TGFβ-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington's Disease.系统遗传学分析揭示了一种跨物种保守的、与应激、睡眠和亨廷顿舞蹈病相关的、依赖转化生长因子β-叉头框蛋白O3的纹状体星形胶质细胞网络。
PLoS Genet. 2016 Jul 8;12(7):e1006137. doi: 10.1371/journal.pgen.1006137. eCollection 2016 Jul.
10
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.
引用本文的文献
1
Current progression in application of extracellular vesicles in central nervous system diseases.细胞外囊泡在中枢神经系统疾病中的应用进展。
Eur J Med Res. 2024 Jan 3;29(1):15. doi: 10.1186/s40001-023-01606-5.
2
Mutant HTT does not affect glial development but impairs myelination in the early disease stage.突变型亨廷顿蛋白不影响神经胶质细胞发育，但在疾病早期会损害髓鞘形成。
Front Neurosci. 2023 Jul 19;17:1238306. doi: 10.3389/fnins.2023.1238306. eCollection 2023.
3
Single-nuclei transcriptome analysis of Huntington disease iPSC and mouse astrocytes implicates maturation and functional deficits.亨廷顿病诱导多能干细胞和小鼠星形胶质细胞的单核转录组分析揭示了成熟和功能缺陷。
iScience. 2022 Dec 6;26(1):105732. doi: 10.1016/j.isci.2022.105732. eCollection 2023 Jan 20.
4
Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases.神经退行性疾病中星形胶质细胞的离子通道功能障碍
Front Physiol. 2022 Feb 9;13:814285. doi: 10.3389/fphys.2022.814285. eCollection 2022.
5
The transcription factor PITX1 drives astrocyte differentiation by regulating the SOX9 gene.转录因子 PITX1 通过调控 SOX9 基因驱动星形胶质细胞分化。
J Biol Chem. 2020 Sep 25;295(39):13677-13690. doi: 10.1074/jbc.RA120.013352. Epub 2020 Aug 5.
6
The far-reaching HAND of cART: cART effects on astrocytes.抗逆转录病毒疗法（cART）的广泛影响：cART对星形胶质细胞的作用
J Neuroimmune Pharmacol. 2021 Mar;16(1):144-158. doi: 10.1007/s11481-020-09907-w. Epub 2020 Mar 9.
7
Astrocytes: Role and Functions in Brain Pathologies.星形胶质细胞：在脑部疾病中的作用与功能
Front Pharmacol. 2019 Sep 27;10:1114. doi: 10.3389/fphar.2019.01114. eCollection 2019.
8
Huntington's Disease Patient-Derived Astrocytes Display Electrophysiological Impairments and Reduced Neuronal Support.亨廷顿舞蹈症患者来源的星形胶质细胞表现出电生理损伤和神经元支持功能降低。
Front Neurosci. 2019 Jun 28;13:669. doi: 10.3389/fnins.2019.00669. eCollection 2019.
9
Diversity of astroglial responses across human neurodegenerative disorders and brain aging.人类神经退行性疾病和大脑衰老中星形胶质细胞反应的多样性。
Brain Pathol. 2017 Sep;27(5):645-674. doi: 10.1111/bpa.12538.
10
Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the HdhQ150/Q150 Mouse Model of Huntington's Disease.在亨廷顿舞蹈病的HdhQ150/Q150小鼠模型中，通过纵向磁共振成像和组织病理学评估行为缺陷与脑病理学之间的相关性。
PLoS One. 2017 Jan 18;12(1):e0168556. doi: 10.1371/journal.pone.0168556. eCollection 2017.
本文引用的文献
1
Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice.星形胶质细胞 Kir4.1 离子通道缺陷导致亨廷顿病模型小鼠神经元功能障碍。
Nat Neurosci. 2014 May;17(5):694-703. doi: 10.1038/nn.3691. Epub 2014 Mar 30.
2
Does size matter in R&D productivity? If not, what does?研发生产力中规模重要吗？如果不重要，那么什么重要呢？
Nat Rev Drug Discov. 2013 Dec;12(12):901-2. doi: 10.1038/nrd4164. Epub 2013 Oct 18.
3
Inflammatory mediators alter the astrocyte transcriptome and calcium signaling elicited by multiple G-protein-coupled receptors.炎症介质改变星形胶质细胞的转录组和多种 G 蛋白偶联受体引起的钙信号。
J Neurosci. 2012 Oct 17;32(42):14489-510. doi: 10.1523/JNEUROSCI.1256-12.2012.
4
Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms.在小鼠脑星形胶质细胞中表达突变型亨廷顿蛋白导致与年龄相关的神经症状。
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22480-5. doi: 10.1073/pnas.0911503106. Epub 2009 Dec 11.
5
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.一个针对星形胶质细胞、神经元和少突胶质细胞的转录组数据库：理解大脑发育和功能的新资源。
J Neurosci. 2008 Jan 2;28(1):264-78. doi: 10.1523/JNEUROSCI.4178-07.2008.
Zotero 插件