JOURNAL ARTICLE

Changes in mitochondrial function in patients with neuromyelitis optica; correlations with motor and cognitive disabilities

Forough Foolad, Fariba Khodagholi, Seyed Massood Nabavi, Mohammad Javan
PloS One 2020, 15 (3): e0230691
32214385

BACKGROUND: 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.

OBJECTIVE: Here we investigated the mitochondrial dysfunction and metabolic alterations in NMO patients and evaluate their correlation with disease progress, disability and cognitive impairment.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

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