Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
PLoS One. 2020 Mar 26;15(3):e0230691. doi: 10.1371/journal.pone.0230691. eCollection 2020.
Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease that mainly affects optic nerves and spinal cord. Besides, loss of motor and cognitive function has been reported as important symptoms of disease.
Here we investigated the mitochondrial dysfunction and metabolic alterations in NMO patients and evaluate their correlation with disease progress, disability and cognitive impairment.
The individuals (12 controls and 12 NMO) were assessed for disease severity by expanded disease status scale (EDSS), cognitive function via symbol digit modalities test (SDMT) and fine motor disability by 9-hole peg test (9-HPT). We have measured Sirtuin 1 (SIRT1), SIRT3, mitochondrial complex I, complex IV, aconitase and α-ketoglutarate dehydrogenase (α-KGD) activity in peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate and cytochrome c (Cyt c) were determined in plasma.
Our results exhibited increased 9-HPT time in NMO patients. 9-HPT results correlated with EDSS; and SDMT negatively correlated with disease duration and number of attacks in patients. Investigation of PBMCs of NMO patients exhibited a decrease of mitochondrial complex I and IV activity that was significant for complex IV. Besides, complex I activity was negatively correlated with 9-HPT time in NMO group. In the plasma samples, a correlation between pyruvate to lactate ratio and EDSS in NMO patients was found and a negative correlation between Cyt c concentration and SDMT was detected.
Our data support the hypothesis that mitochondrial dysfunction occurred in the CNS and the peripheral blood may contribute to disease progress, disability level and the cognitive impairment in NMO patients.
视神经脊髓炎（NMO）是一种主要影响视神经和脊髓的炎症性脱髓鞘疾病。此外，运动和认知功能的丧失已被报道为疾病的重要症状。
本研究旨在探讨 NMO 患者的线粒体功能障碍和代谢改变，并评估其与疾病进展、残疾和认知障碍的相关性。
通过扩展疾病状况量表（EDSS）评估个体（12 名对照和 12 名 NMO 患者）的疾病严重程度，通过符号数字模态测验（SDMT）评估认知功能，通过 9 孔钉测试（9-HPT）评估精细运动障碍。我们测量了外周血单核细胞（PBMCs）中的 Sirtuin 1（SIRT1）、SIRT3、线粒体复合物 I、复合物 IV、顺乌头酸酶和α-酮戊二酸脱氢酶（α-KGD）活性。此外，还测定了血浆中的 SIRT1、丙酮酸、乳酸和细胞色素 c（Cyt c）。
我们的研究结果表明，NMO 患者的 9-HPT 时间延长。9-HPT 结果与 EDSS 相关；SDMT 与患者的疾病持续时间和发作次数呈负相关。对 NMO 患者 PBMCs 的研究表明，线粒体复合物 I 和 IV 的活性降低，其中复合物 IV 的活性降低更为显著。此外，NMO 组中复合物 I 的活性与 9-HPT 时间呈负相关。在血浆样本中，发现 NMO 患者的丙酮酸与乳酸比值与 EDSS 之间存在相关性，并且 Cyt c 浓度与 SDMT 之间存在负相关。
我们的数据支持这样一种假设，即中枢神经系统和外周血中的线粒体功能障碍可能导致 NMO 患者的疾病进展、残疾程度和认知障碍。
