当前位置: X-MOL 学术Genes Brain Behav. › 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.)
Fragile X-associated tremor/ataxia syndrome: Regional decrease of mitochondrial DNA copy number relates to clinical manifestations.
Genes, Brain and Behavior ( IF 2.4 ) Pub Date : 2019-05-24 , DOI: 10.1111/gbb.12565
Maria I Alvarez-Mora 1, 2, 3 , Petar Podlesniy 4, 5 , Ellen Gelpi 3, 6, 7 , Renate Hukema 8 , Irene Madrigal 1, 2, 3 , Javier Pagonabarraga 9 , Ramon Trullas 3, 4, 5 , Montserrat Mila 1, 2, 3 , Laia Rodriguez-Revenga 1, 2, 3
Affiliation  

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that appears in at least one-third of adult carriers of a premutation (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene. Several studies have shown that mitochondrial dysfunction may play a central role in aging and also in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease as well as in FXTAS. It has been recently proposed that mtDNA copy number, measured by the number of mitochondrial genomes per nuclear genome (diploid), could be a useful biomarker of mitochondrial dysfunction. In order to elucidate the role of mtDNA variation in the pathogenesis of FXTAS, mtDNA copy number was quantified by digital droplet Polymerase chain reaction. In human brain samples, mtDNA levels were measured in the cerebellar vermis, dentate nucleus, parietal and temporal cortex, thalamus, caudate nucleus and hippocampus from a female FXTAS patient, a FMR1 premutation male carrier without FXTAS and from three male controls. The mtDNA copy number was further analyzed using this technology in dermal fibroblasts primary cultures derived from three FXTAS patients and three controls as well as in cortex and cerebellum of a CGG knock in FXTAS mice model. Finally, qPCR was carried out in human blood samples. Results indicate reduced mtDNA copy number in the specific brain region associated with disease progression in FXTAS patients, providing new insights into the role of mitochondrial dysfunction in the pathogenesis of FXTAS.

中文翻译:

脆性X相关震颤/共济失调综合征:线粒体DNA拷贝数的区域减少与临床表现有关。

脆性X相关性震颤/共济失调综合征(FXTAS)是一种迟发性神经退行性疾病,至少出现在脆性X智力低下1(FMR1)基因中一个预先突变(55-200个CGG重复)的成年携带者中,至少有三分之一。几项研究表明,线粒体功能障碍可能在衰老以及神经退行性疾病(例如阿尔茨海默氏病,帕金森氏病,亨廷顿氏病以及FXTAS)中发挥重要作用。最近有人提出,通过每个核基因组(二倍体)的线粒体基因组数量来衡量的mtDNA拷贝数可能是线粒体功能障碍的有用生物标志物。为了阐明mtDNA变异在FXTAS发病机理中的作用,通过数字液滴聚合酶链反应对mtDNA的拷贝数进行了定量。在人脑样本中 从女性FXTAS患者,无FXTAS的FMR1突变男性携带者和三个男性对照的小脑ver,齿状核,顶叶和颞皮层,丘脑,尾状核和海马中测量mtDNA水平。使用该技术,在来自三名FXTAS患者和三名对照的真皮成纤维细胞原代培养物中以及在FXTAS小鼠模型的CGG敲除的皮质和小脑中进一步分析了mtDNA拷贝数。最后,在人血样品中进行qPCR。结果表明,与FXTAS患者疾病进展相关的特定大脑区域中mtDNA拷贝数减少,为线粒体功能障碍在FXTAS发病机理中的作用提供了新见解。一名女性FXTAS患者,一名没有FXTAS的FMR1突变男性携带者和三个男性对照的尾状核和海马体。使用该技术,在来自三名FXTAS患者和三名对照的真皮成纤维细胞原代培养物中以及在FXTAS小鼠模型的CGG敲除的皮质和小脑中进一步分析了mtDNA拷贝数。最后,在人血样品中进行qPCR。结果表明,与FXTAS患者疾病进展相关的特定大脑区域中mtDNA拷贝数减少,为线粒体功能障碍在FXTAS发病机理中的作用提供了新见解。一名女性FXTAS患者,一名没有FXTAS的FMR1突变男性携带者和三个男性对照的尾状核和海马体。使用该技术,在来自三名FXTAS患者和三名对照的真皮成纤维细胞原代培养物中以及在FXTAS小鼠模型的CGG敲除的皮质和小脑中进一步分析了mtDNA拷贝数。最后,在人血样品中进行qPCR。结果表明,与FXTAS患者疾病进展相关的特定大脑区域中mtDNA拷贝数减少,为线粒体功能障碍在FXTAS发病机理中的作用提供了新见解。使用该技术,在来自三名FXTAS患者和三名对照的真皮成纤维细胞原代培养物中以及在FXTAS小鼠模型的CGG敲除的皮质和小脑中进一步分析了mtDNA拷贝数。最后,在人血样品中进行qPCR。结果表明,与FXTAS患者疾病进展相关的特定大脑区域中mtDNA拷贝数减少,为线粒体功能障碍在FXTAS发病机理中的作用提供了新见解。使用该技术,在来自三名FXTAS患者和三名对照的真皮成纤维细胞原代培养物中以及在FXTAS小鼠模型的CGG敲除的皮质和小脑中进一步分析了mtDNA拷贝数。最后,在人血样品中进行qPCR。结果表明,与FXTAS患者疾病进展相关的特定大脑区域中mtDNA拷贝数减少,为线粒体功能障碍在FXTAS发病机理中的作用提供了新见解。
更新日期:2019-11-01
down
wechat
bug