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帕金森病认知谱中肌肉线粒体呼吸链表型分析的可行性。

The feasibility of muscle mitochondrial respiratory chain phenotyping across the cognitive spectrum in Parkinson's disease.

机构信息

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.

NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; AGE Research Group, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle upon Tyne, United Kingdom.

出版信息

Exp Gerontol. 2020 Sep;138:110997. doi: 10.1016/j.exger.2020.110997. Epub 2020 Jun 15.

DOI:10.1016/j.exger.2020.110997
PMID:
32554091
Abstract

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 τ 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) τ 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.

摘要

简介

骨骼肌减少症是一种进行性的骨骼肌疾病,与帕金森病(PD)等与年龄相关的神经退行性疾病之间的关系研究较少。

目的

我们旨在确定:1)在 PD 患者中,肌肉骨骼与认知功能的关系;2)肌肉线粒体呼吸链(MRC)功能和含量是否在老年 PD 患者中得到保留。

方法

使用握力、椅子上升和生物阻抗分析来定义骨骼肌减少症。通过估计有氧运动后小腿肌肉中 τ PCr(s)(磷酸肌酸半衰期恢复),使用磷磁共振波谱(MRS)评估 MRC 功能。对股外侧肌进行活检,并通过荧光免疫组化评估孔蛋白和 MRC 复合物 I 和 IV 的成分来评估 MRC 含量。

结果

共招募了 9 名参与者(78%为男性;平均年龄 79.9 岁;PD 病程 3.3 年)。其中 4 人认知障碍。6 人患有可能的骨骼肌减少症。8 名参与者完成了 MRS,平均(SD) τ PCr 为 37.8(7.6)秒,表明线粒体功能正常。所有参与者均获得了肌肉活检,且该过程耐受性良好。孔蛋白 Z 分数(代表线粒体质量的指标)低于对照组(0-89%的纤维低孔蛋白)。复合物 I(0.16-4.59%)和复合物 IV(0-3.79%)的缺乏程度较小。

结论

在 PD 患者的认知功能范围内,详细的表型分析、肌肉活检和成像是可行且可接受的。骨骼肌减少症较为常见,可能与较低的线粒体质量和较低水平的 MRC 缺陷有关。

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