Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria
| Autor: | Antonella Gorini, Fabio Tascedda, Federica Ferrari, Nicoletta Brunello, Roberto Federico Villa |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Proteomics 0301 basic medicine medicine.medical_specialty Proteome Bioenergetics Antidepressive Agents Tricyclic Pharmacology Biology Mitochondrion Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine In vivo Fluoxetine Internal medicine Desipramine medicine Animals 5-HT receptor Neuroscience (all) General Neuroscience Succinate dehydrogenase Brain energy metabolism Frontal Lobe Mitochondria Metabolic pathway 030104 developmental biology Endocrinology Functional Proteomics biology.protein Antidepressive Agents Second-Generation Energy Metabolism 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuroscience. 330:326-334 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2016.05.051 |
| Popis: | Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed. Antidepressants in vivo treatment modified the activities of selected enzymes of different mitochondria, leading to metabolic modifications in the energy metabolism of brain cortex: (a) the enhancement of cytochrome oxidase activity on somatic mitochondria; (b) the decrease of malate, succinate dehydrogenase and glutamate-pyruvate transaminase activities of synaptic mitochondria; (c) the selective effect of fluoxetine on enzymes related to glutamate metabolism. These results overcome the conflicting data so far obtained with antidepressants on brain energy metabolism, because the enzymatic analyses were made on mitochondria with diversified neuronal in vivo localization, i.e. on somatic and synaptic. This research is the first investigation on the pharmacodynamics of antidepressants studied at subcellular level, in the perspective of (i) assessing the role of energy metabolism of cerebral mitochondria in animal models of mood disorders, and (ii) highlighting new therapeutical strategies for antidepressants targeting brain bioenergetics. |
| Databáze: | OpenAIRE |
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