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The feasibility of muscle mitochondrial respiratory chain phenotyping across the cognitive spectrum in Parkinson's disease.
Experimental Gerontology ( IF 3.9 ) Pub Date : 2020-06-15 , DOI: 10.1016/j.exger.2020.110997
Alison J Yarnall 1 , Antoneta Granic 2 , Samantha Waite 3 , Kieren G Hollingsworth 4 , Charlotte Warren 5 , Amy E Vincent 5 , Doug M Turnbull 6 , Robert W Taylor 6 , Richard M Dodds 2 , Avan A Sayer 2
Affiliation  

Introduction

There has been little work on the relationship between sarcopenia, a progressive skeletal muscle disorder, and age-related neurodegenerative diseases such as Parkinson's disease (PD).

Objectives

We aimed to determine: 1) the feasibility of characterizing skeletal muscle across a range of cognitive function in PD; 2) if muscle mitochondrial respiratory chain (MRC) function and content are preserved in older adults with PD.

Methods

Sarcopenia was defined using handgrip strength, chair rise and bioimpedance analysis. MRC function was assessed using phosphorous magnetic resonance spectroscopy (MRS) by estimating τ1/2 PCr (s) (phosphocreatine half-time recovery) in the calf muscles following a bout of aerobic exercise. Biopsy of the vastus lateralis muscle was performed, and MRC content assessed by fluorescent immunohistochemistry for porin and components of MRC Complexes I and IV.

Results

Nine participants (78% male; mean age 79.9; PD duration 3.3 years) were recruited. Four had cognitive impairment. Six participants had probable sarcopenia. Eight participants completed MRS and had mean (SD) τ1/2 PCr of 37.8 (7.6) seconds, suggesting preserved mitochondrial function. Muscle biopsies were obtained in all and the procedure was well tolerated. Porin Z-score, a proxy for mitochondrial mass, was lower than expected compared to controls (0–89% of fibres with low porin). There was a small amount of Complex I (0.16–4.59%) and Complex IV (0–3.79%) deficiency.

Conclusions

Detailed phenotyping, muscle biopsy and imaging was feasible and acceptable across a spectrum of cognitive function in PD. Sarcopenia was relatively common and may be associated with lower mitochondrial mass and low levels of MRC deficiency.



中文翻译:

在帕金森氏病中跨认知谱线的线粒体呼吸链表型的可行性。

介绍

关于肌肉减少症,进行性骨骼肌疾病和与年龄有关的神经退行性疾病(如帕金森氏病(PD))之间的关系的研究很少。

目标

我们旨在确定:1)在PD的一系列认知功能中表征骨骼肌的可行性;2)在患有PD的老年人中,是否保留了肌肉线粒体呼吸链(MRC)的功能和含量。

方法

肌肉减少症通过握力,椅子抬高和生物阻抗分析来定义。在进行有氧运动后,通过评估小腿肌肉中的τ1 /2 PCr(s)(磷酸肌酸的半衰期恢复),使用磷磁共振波谱(MRS)评估了MRC功能。进行股外侧肌的活检,并通过荧光免疫组织化学评估MRC复合物I和IV的孔蛋白和组分的MRC含量。

结果

招募了九名参与者(男性78%;平均年龄79.9; PD病程3.3年)。四个有认知障碍。六名参与者可能患有肌肉减少症。八名参与者完成了MRS,平均(SD)τ1 /2 PCr为37.8(7.6)秒,表明线粒体功能得以保留。全部获得了肌肉活检,并且该过程被良好耐受。线粒体质量的代表蛋白Z评分比对照(0-89%的低孔蛋白纤维)要低。少量的复合物I(0.16-4.59%)和复合物IV(0-3.79%)缺乏。

结论

在PD的一系列认知功能中,详细的表型分析,肌肉活检和成像是可行的并且可以接受。肌肉减少症相对常见,可能与线粒体质量降低和MRC缺乏水平低有关。

更新日期:2020-06-23
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