Wellcome Trust Centre for Mitochondrial Research, Newcastle University, Framlington Place, Newcastle upon Tyne.
Neuropathol Appl Neurobiol. 2013 Jun;39(4):377-89. doi: 10.1111/j.1365-2990.2012.01290.x.
Although mitochondrial abnormalities have been reported within paraspinal muscles in patients with axial weakness and neuromuscular disease as well as with ageing, the basis of respiratory deficiency in paraspinal muscles is not known. This study aimed to determine the extent and basis of respiratory deficiency in paraspinal muscles from cases undergoing surgery for degenerative spinal disease and post mortem cases without a history of spinal disease, where age-related histopathological changes were previously reported.
Cervical and lumbar paraspinal muscles were obtained peri-operatively from 13 patients and from six post mortem control cases (age range 18-82 years) without a neurological disease. Sequential COX/SDH (mitochondrial respiratory chain complex IV/complex II) histochemistry was performed to identify respiratory-deficient muscle fibres (lacking complex IV with intact complex II activity). Real-time polymerase chain reaction, long-range polymerase chain reaction and sequencing were used to identify and characterize mitochondrial DNA (mtDNA) deletions and determine mtDNA copy number status. Mitochondrial respiratory chain complex subunits were detected by immunohistochemistry.
The density of respiratory-deficient fibres increased with age. On average, 3.96% of fibres in paraspinal muscles were respiratory-deficient (range 0-10.26). Respiratory deficiency in 36.8% of paraspinal muscle fibres was due to clonally expanded mtDNA deletions. MtDNA depletion accounted for further 13.5% of respiratory deficiency. The profile of immunohistochemically detected subunits of complexes was similar in respiratory-deficient fibres with and without mtDNA deletions or mtDNA depletion.
Paraspinal muscles appeared to be particularly susceptible to age-related mitochondrial respiratory chain defects. Clonally expanded mtDNA deletions and focal mtDNA depletion may contribute towards the development of age-related postural abnormalities.
尽管在患有轴性无力和神经肌肉疾病以及衰老的患者的脊柱旁肌肉中已经报道了线粒体异常，但脊柱旁肌肉呼吸功能缺陷的基础尚不清楚。本研究旨在确定接受退行性脊柱疾病手术的病例和无脊柱疾病病史的尸检病例的脊柱旁肌肉的呼吸缺陷的程度和基础，先前有报道称这些病例存在与年龄相关的组织病理学变化。
从 13 名患者和 6 名无神经疾病的尸检对照病例（年龄范围 18-82 岁）手术期间获得颈和腰脊柱旁肌肉。进行连续 COX/SDH（线粒体呼吸链复合物 IV/复合物 II）组织化学染色以鉴定呼吸缺陷纤维（缺乏复合物 IV 但具有完整的复合物 II 活性）。实时聚合酶链反应、长距离聚合酶链反应和测序用于鉴定和表征线粒体 DNA（mtDNA）缺失并确定 mtDNA 拷贝数状态。通过免疫组织化学检测线粒体呼吸链复合亚基。
呼吸缺陷纤维的密度随年龄增加而增加。平均而言，脊柱旁肌肉中有 3.96%的纤维存在呼吸缺陷（范围 0-10.26%）。36.8%的脊柱旁肌肉纤维的呼吸缺陷是由于克隆性扩张的 mtDNA 缺失引起的。mtDNA 耗竭占进一步的 13.5%的呼吸缺陷。具有和不具有 mtDNA 缺失或 mtDNA 耗竭的呼吸缺陷纤维中免疫组织化学检测到的复合物亚基的图谱相似。
脊柱旁肌肉似乎特别容易受到与年龄相关的线粒体呼吸链缺陷的影响。克隆性扩张的 mtDNA 缺失和局灶性 mtDNA 耗竭可能导致与年龄相关的姿势异常的发展。
