Effects of antidepressants and depressive disorders on mitochondrial functions

• Thesis title in Czech: Vliv antidepresiv a depresivní poruchy na mitochondriální funkce
• Thesis title in English: Effects of antidepressants and depressive disorders on mitochondrial functions
• Key words: antidepresiva, stabilizátory nálady, deprese, mitochondrie, elektronový transportní řetězec, citrátový cyklus, oxidativní fosforylace
• English key words: antidepressants, mood stabilizers, depression, mitochondria, electron transport chain, citric acid cycle, oxidative phosphorylation
• Academic year of topic announcement: 2011/2012
• Thesis type: dissertation
• Thesis language: angličtina
• Department: Department of Psychiatry First Faculty of Medicine Charles University and General University Hospital in Prague (11-00610)
• Supervisor: prof. RNDr. Zdeněk Fišar, CSc.
• Author: hidden - assigned and confirmed by the Study Dept.
• Date of registration: 20.06.2012
• Date of assignment: 20.06.2012
• Confirmed by Study dept. on: 20.06.2012
• Date and time of defence: 24.09.2012 08:30
• Venue of defence: Neurologická klinika 1. LF
• Date of electronic submission: 22.06.2012
• Date of proceeded defence: 24.09.2012
• Course: Defence of the dissertation (B90002)
• Opponents: prof. MUDr. Pavel Martásek, DrSc.

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Preliminary scope of work

V tomto projektu byly studovány jednak in vitro účinky různých antidepresiv a stabilizátorů nálady na mitochondriální funkce, jednak změny vybraných mitochondriálních funkcí osob s depresivními poruchami. Měření byla prováděna nejprve na izolovaných mitochondriích ze zvířecích mozků (in vitro model), poté na krevních destičkách depresivních pacientů. Byly měřeny účinky farmakologicky odlišných antidepresiv a stabilizátorů nálady na mitochondrie izolované ze zvířecích mozků (in vitro model). Aktivita izoforem monoaminooxidasy (MAO) byla stanovena radiochemicky, aktivity dalších mitochondriálních enzymů spektrofotometricky. Celková aktivita systému oxidační fosforylace byla určena respirometrií s vysokým rozlišením. Metody byly modifikovány pro měření stejných parametrů v krevních destičkách u pacientů s depresivní epizodou a u zdravých kontrol. Cílem projektu bylo zjistit, zda jsou mitochondriální funkce antidepresivy, stabilizátory nálady a depresí významně ovlivněny a zda mohou být využity jako prediktory odezvy na léčbu antidepresivy nebo biologické markery depresivní poruchy.

Preliminary scope of work in English

In our project, in vitro effects of pharmacologically different antidepressants and mood-stabilisators on mitochondrial functions were studied as well as selected mitochondrial functions in patients with depressive disorders. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high-resolution respirometry. Methods were modified to measure the same parameters in blood platelets of patients with depressive episode and healthy controls. The aim of the study was to find out, whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression, and can be further used as biological markers of depressive disorders.