Piotr Czarny1, Paulina Wigner2, Justyna Strycharz1, Ewa Swiderska1, Ewelina Synowiec2, Magdalena Szatkowska2, Agnieszka Sliwinska3, Monika Talarowska4, Janusz Szemraj1, Kuan-Pin Su5, Michael Maes6,7,8, Tomasz Sliwinski2, Piotr Galecki4. 1. Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland. 2. Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. 3. Department of Nucleic Acids Biochemistry, Medical University of Lodz, Lodz, Poland. 4. Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland. 5. Department of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan. 6. School of Medicine, Barwon Health, IMPACT Strategic Research Centre Deakin University, Geelong, Australia. 7. Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand. 8. Health Sciences Graduate Program Health Sciences Center, State University of Londrina, Londrina, Brazil.
Abstract
Objectives: We aimed to explore mitochondrial DNA (mtDNA) copy number, damage, repair and degradation in peripheral blood mononuclear cells (PBMCs) of patients with depression and to compare the results with healthy subjects. Methods: Total genomic DNA was isolated from PBMCs of 25 depressed and 60 healthy subjects before, immediately after, and 3 h after the exposure to H2O2. Evaluation of mtDNA copy number was performed using real-time PCR and 2-ΔCt methods. Semi-long run real-time PCR was used to estimate the number of mtDNA lesions. Results: Baseline mtDNA copy number did not differ in cells of healthy and depressed subjects; however, it was negatively correlated with the severity of the episode. After a 10-min challenge with hydrogen peroxide (H2O2), depressed patients' PBMCs exhibited slower changes of the copy number, indicating a lower efficiency of mtDNA degradation compared to controls. Moreover, a significantly higher number of mtDNA lesions was found in depressed patients at the baseline as well as at other experimental time points. mtDNA lesions were also elevated in depressed patient cells immediately after H2O2 exposure. Induction of oxidative stress had no significant influence on the cells of controls.Conclusions: We are the first to show that impairment in repair and degradation of mtDNA may be involved in the pathophysiology of depression.
Objectives: We aimed to explore mitochondrial DNA (mtDNA) copy number, damage, repair and degradation in peripheral blood mononuclear cells (PBMCs) of patients with depression and to compare the results with healthy subjects. Methods: Total genomic DNA was isolated from PBMCs of 25 depressed and 60 healthy subjects before, immediately after, and 3 h after the exposure to H2O2. Evaluation of mtDNA copy number was performed using real-time PCR and 2-ΔCt methods. Semi-long run real-time PCR was used to estimate the number of mtDNA lesions. Results: Baseline mtDNA copy number did not differ in cells of healthy and depressed subjects; however, it was negatively correlated with the severity of the episode. After a 10-min challenge with hydrogen peroxide (H2O2), depressedpatients' PBMCs exhibited slower changes of the copy number, indicating a lower efficiency of mtDNA degradation compared to controls. Moreover, a significantly higher number of mtDNA lesions was found in depressedpatients at the baseline as well as at other experimental time points. mtDNA lesions were also elevated in depressedpatient cells immediately after H2O2 exposure. Induction of oxidative stress had no significant influence on the cells of controls.Conclusions: We are the first to show that impairment in repair and degradation of mtDNA may be involved in the pathophysiology of depression.
Entities:
Keywords:
Depression; mitochondrial DNA copy number; mitochondrial DNA damage; mitochondrial DNA degradation; mitochondrial DNA repair
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Authors: Katarzyna Bialek; Piotr Czarny; Cezary Watala; Paulina Wigner; Monika Talarowska; Piotr Galecki; Janusz Szemraj; Tomasz Sliwinski Journal: PeerJ Date: 2020-02-25 Impact factor: 2.984