Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. 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...

Dans le cadre de la fusion par confinement inertiel, une capsule contenant le combustible de deutérium-tritium est implosée soit par irradiation laser (attaque directe, interaction laser – cible de numéro atomique faible), soit par un rayonnement de corps noir émis par une cavité convertissant le rayonnement laser (attaque indirecte, interaction laser – cible de numéro atomique élevé).Dans les deux cas, une modélisation correcte du transport électronique est cruciale pour avoir des simulations hydro-radiatives prédictives. Cependant, il a été montré très tôt que les hypothèses d'un mécanisme de transport linéaire ne sont pas applicables dans le cadre de l'irradiation d'une cible solide par un laser de puissance (I~10^14 W/cm²). Cela est dû d'une part à des gradients de température très importants (effets cinétiques dits « non-locaux ») ainsi qu'à la présence d'un champ magnétique auto-généré par effet thermo-électrique. Enfin, le flux de chaleur et le champ magnétique sont fortement couplés au travers de deux mécanismes : le transport du champ magnétique par le flux de chaleur (effet Nernst) et la rotation et inhibition du flux de chaleur par la magnétisation du plasma (effet Righi-Leduc).Dans le présent manuscrit, nous commencerons par exposer les différents modèles de transport électronique, et en particulier le modèle non-local avec champ magnétique, implémenté dans le code hydro-radiatif FCI2. Par la suite, nous chercherons à valider ce modèle par des comparaisons avec un code cinétique, puis avec une expérience lors de laquelle le champ magnétique a été mesuré par radiographie proton. Cela fait, nous utiliserons le code FCI2 pour expliquer la source et le transport du champ, ainsi que son effet sur l'interaction.Enfin, nous étudierons la reconnexion du champ magnétique, lors de l'irradiation d'une cible par deux faisceaux lasers. / In the framework of the inertial confinement fusion, a pellet filled with the deuterium-tritium fuel is imploded, either through laser irradiation (direct drive, laser – low atomic number target interaction) or by the black body radiation from a cavity converting the laser radiation (indirect drive, laser – high atomic number target interaction).In both cases, a correct modeling of the electron transport is of first importance in order to have predictive hydro-radiative simulations. Nonetheless, it has been shown early on that the hypothesis of the linear transport are not valid in the framework of a solid target irradiated by a high power laser (I~1014 W/cm²). This is due in part to very steep temperature gradients (kinetic effects, so-called « non-local ») and because of a magnetic field self-generated through the thermo-electric effect. Finally, the heat flux and the magnetic field are strongly coupled through two mecanisms: the advection of the field with the heat flux (Nernst effect) and the rotation and inhibition of the heat flux by the plasma's magnetization (Righi-Leduc effect).In this manuscript, we will first present the various electron transport models, particularly the non-local with magnetic field model included in the hydro-radiative code FCI2. Following, in order to validate this model, we will compare it first against a kinetic code, and then with an experiment during which the magnetic field has been probed through proton radiography. Once the model validated, we will use FCI2 simulations to explain the source and transport of the field, as well as its effect on the interaction.Finally, the reconnection of the magnetic field, during the irradiation of a solid target by two laser beams, will be studied.

Mitochondria are essential organelles for most eukaryotic cells, containing intricate networks of numerous proteins. These include, among others, complexes I-IV of the electron transport chain. Being at the crossroads of the tricarboxylic acid cycle and the respiratory chain, mitochondrial complex II plays a key role in cellular metabolism. The protein complex, also known as succinate dehydrogenase, is capable of not only succinate oxidation and electron transfer but also contributes to the production of reactive oxygen species. Mitochondrial complex II consists of four subunits, SDHA-D, and four dedicated protein assembly factors SDHAF1-4 that participate in complex II biogenesis. Mutations and epigenetic modulations of genes coding for succinate dehydrogenase subunits or assembly factors are associated with pathological conditions such as neurodegenerative diseases, or may result in tumor formation. However, inborn complex-II-linked mitochondrial pathologies are rather understudied, compared to diseases with causative errors of other mitochondrial complexes, presumably due to the fact that none of complex II subunits is encoded in the mitochondrial genome. Recent studies have shown that impairment of mitochondrial complex II function or assembly leads to accumulation of alternative assembly forms...

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Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...

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