Nielsen 2016 Abstract IOC116

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Nielsen B, Woertwein G, Cejvanovic V, Hansen AR, Weimann A, Bjerring PN, Poulsen HE, Joergensen MB (2016) The function of mitochondria and oxidative stress after antidepressants treatment in rats. Mitochondr Physiol Network 21.11

Link: Mitochondr Physiol Network 21.11

Nielsen B, Woertwein G, Cejvanovic V, Hansen AR, Weimann A, Bjerring PN, Poulsen HE, Joergensen MB (2016)

Event: IOC116

Major depressive disorder (MDD) affects 350 million people worldwide and is a leading contributor to the global burden of diseases. Evidence show that impaired mitochondrial function contributes to the pathogenesis of MDD via different pathways including reactive oxygen species (ROS). An increase in ROS will influence the mitochondrial membrane potential and might trigger a “ROS-induced ROS-release” (RIRR), which can be involved in the pathogenesis of MDD.

Electroconvulsive therapy (ECT) is a very effective treatment for MDD. Studies have shown an increased energy load of the mitochondrial electron transfer-pathway resulting in superoxide production following seizures. Another source of ROS is monoamine oxidase (MAO) which is bound to the outer membrane of mitochondria and ensures the right functioning of synaptic neurotransmission through oxidative deamination of monoamines such as serotonin and dopamine. MAO is therefore critical in regulating behavior and emotions and MAO-inhibitors are used for the treatment of depression. Since ROS are part of both these therapeutic interventions they may be involved in both effects and side effects of the treatments. The aim with this study was to determine the level of oxidative stress after chronic electroconvulsive shock (ECS) and investigate the effects of an irreversible monoamine oxidase inhibitor, phenelzine (PHZ), on the mitochondrial production of reactive oxygen species.

The rats received 9 ECS over a period of three weeks mimicking the clinical treatment and were sacrificed three days after the last ECS. Another group of rats received PHZ I.P. every day for 14 days and was sacrificed the day after the last treatment. The cortex piriformis of the brain was dissected and a homogenate was made for the high-resolution respirometry (Oroboros Instruments). Within five min after decapitation the homogenate was in the respirometer. Cortex piriformis was also used for analyzing the oxidative damage of RNA, 8-oxo-7,8-dihydroguanosine, using ultraperfomance liquid chromatography and tandem mass spectrometry (UPLC MS/MS).

This study is currently ongoing and preliminary results will be presented at IOC116.

Labels: MiParea: Respiration  Pathology: Other 

Organism: Rat  Tissue;cell: Nervous system  Preparation: Homogenate  Enzyme: TCA cycle and matrix dehydrogenases  Regulation: Aerobic glycolysis, Flux control 

HRR: Oxygraph-2k, O2k-Fluorometer 

Ultraperfomance liquid chromatography and tandem mass spectrometry (UPLC MS/MS) 


Lab Neuropsych, Dept Psych; Dept Clinical Pharmacol Q; Copenhagen Univ Hospital, DK. -