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CNS & Neurological Disorders - Drug Targets

Author(s): Jana Hroudová*, Zdeněk Fišar, Hana Hansíková, Lucie Kališová, Eva Kitzlerová, Martina Zvěřová, Alena Lambertová and Jiří Raboch

DOI: 10.2174/1871527318666181224130011

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Mitochondrial Dysfunction in Blood Platelets of Patients with Manic Episode of Bipolar Disorder

Page: [222 - 231] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Objectives: The bipolar affective disorder (BAD) pathophysiology is multifactorial and has not been fully clarified.

Method: We measured selected mitochondrial parameters in peripheral blood components. The analyses were performed for patients suffering from a manic episode during remission and were compared to those performed for healthy controls. BAD was clinically evaluated using well-established diagnostic scales and questionnaires. Mitochondrial respiration was examined in intact and permeabilized blood platelets using high-resolution respirometry. The citrate synthase (CS) and electron transport system (ETS) complex (complex I, II, and IV) activities were examined in platelets.

Results: The CS, complex II and complex IV activities were decreased in the BAD patients, complex I activity was increased, and the ratio of complex I to CS was significantly increased. In the intact platelets, respiration after complex I inhibition and residual oxygen consumption were decreased in the BAD patients compared to the healthy controls. In the permeabilized platelets, a decreased ETS capacity was found in the BAD patients. No significant differences were found between BAD patients in mania and remission.

Conclusion: Increased complex I activity can be a compensatory mechanism for decreased CS and complex II and IV activities. We conclude that complex I and its abnormal activity contribute to defects in cellular energy metabolism during a manic episode and that the deficiency in the complex's functioning, but not the availability of oxidative phosphorylation substrates, seems to be responsible for the decreased ETS capacity in BAD patients. The observed parameters can be further evaluated as ‘trait’ markers of BAD.

Keywords: Bipolar affective disorder, blood platelet, electron transport chain complexes, mania, mitochondrion, respiratory rate.

Graphical Abstract

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