当前位置: X-MOL 学术Proc. Natl. Acad. Sci. U.S.A. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington’s disease [Neuroscience]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-05-11 , DOI: 10.1073/pnas.2020293118
Foteini Paraskevopoulou 1, 2 , Poorya Parvizi 3 , Gökçe Senger 3 , Nurcan Tuncbag 3, 4, 5 , Christian Rosenmund 2, 6 , Ferah Yildirim 7, 8
Affiliation  

Transcriptional dysregulation in Huntington’s disease (HD) causes functional deficits in striatal neurons. Here, we performed Patch-sequencing (Patch-seq) in an in vitro HD model to investigate the effects of mutant Huntingtin (Htt) on synaptic transmission and gene transcription in single striatal neurons. We found that expression of mutant Htt decreased the synaptic output of striatal neurons in a cell autonomous fashion and identified a number of genes whose dysregulation was correlated with physiological deficiencies in mutant Htt neurons. In support of a pivotal role for epigenetic mechanisms in HD pathophysiology, we found that inhibiting histone deacetylase 1/3 activities rectified several functional and morphological deficits and alleviated the aberrant transcriptional profiles in mutant Htt neurons. With this study, we demonstrate that Patch-seq technology can be applied both to better understand molecular mechanisms underlying a complex neurological disease at the single-cell level and to provide a platform for screening for therapeutics for the disease.



中文翻译:

在亨廷顿病中通过 Patch-seq 在单个神经元中研究抑制性 GABA 能突触传递和转录受损 [神经科学]

亨廷顿病 (HD) 中的转录失调导致纹状体神经元功能缺陷。在这里,我们在体外 HD 模型中进行了补丁测序 (Patch-seq),以研究突变亨廷顿 (Htt) 对单个纹状体神经元突触传递和基因转录的影响。我们发现突变Htt 的表达以细胞自主方式降低纹状体神经元的突触输出,并鉴定了许多基因,其失调与突变 Htt 神经元的生理缺陷相关。为了支持表观遗传机制在 HD 病理生理学中的关键作用,我们发现抑制组蛋白去乙酰化酶 1/3 活动纠正了几种功能和形态缺陷,并减轻了突变 Htt 神经元中的异常转录谱。通过这项研究,我们证明了 Patch-seq 技术既可以用于在单细胞水平上更好地理解复杂神经疾病的分子机制,也可以为筛选该疾病的治疗方法提供平台。

更新日期:2021-05-06
down
wechat
bug