Mitochondrial energy metabolism of rat hippocampus after treatment with the antidepressants desipramine and fluoxetine
| Autor: | Fabio Tascedda, Antonella Gorini, Nicoletta Brunello, Roberto Federico Villa, Federica Ferrari, Laura Bagini |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Bioenergetics Mitochondrion Pharmacology Hippocampus Electron Transport Complex IV Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Glutamate Dehydrogenase Desipramine Internal medicine Fluoxetine medicine Cytochrome c oxidase Animals 5-HT receptor Cytochrome Reductases Analysis of Variance Functional proteomics biology Chemistry Glutamate dehydrogenase Metabolism Brain energy metabolism Antidepressive Agents Mitochondria Rats 030104 developmental biology Endocrinology biology.protein Energy Metabolism 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropharmacology. 121 |
| ISSN: | 1873-7064 |
| Popis: | Alterations in mitochondrial functions have been hypothesized to participate in the pathogenesis of depression, because brain bioenergetic abnormalities have been detected in depressed patients by neuroimaging in vivo studies. However, this hypothesis is not clearly demonstrated in experimental studies: some suggest that antidepressants are inhibitors of mitochondrial metabolism, while others observe the opposite. In this study, the effects of 21-day treatment with desipramine (15 mg/kg) and fluoxetine (10 mg/kg) were examined on the energy metabolism of rat hippocampus, evaluating the catalytic activity of regulatory enzymes of mitochondrial energy-yielding metabolic pathways. Because of the micro-heterogeneity of brain mitochondria, we have distinguished between (a) non-synaptic mitochondria (FM) of neuronal perikaryon (post-synaptic compartment) and (b) intra-synaptic light (LM) and heavy (HM) mitochondria (pre-synaptic compartment). Desipramine and fluoxetine changed the catalytic activity of specific enzymes in the different types of mitochondria: (a) in FM, both drugs enhanced cytochrome oxidase and glutamate dehydrogenase, (b) in LM, the overall bioenergetics was unaffected and (c) in HM only desipramine increased malate dehydrogenase and decreased the activities of Electron Transport Chain Complexes. These results integrate the pharmacodynamic features of desipramine and fluoxetine at subcellular level, overcoming the previous conflicting data about the effects of antidepressants on brain energy metabolism, mainly referred to whole brain homogenates or to bulk of cerebral mitochondria. With the differentiation in non-synaptic and intra-synaptic mitochondria, this study demonstrates that desipramine and fluoxetine lead to adjustments in the mitochondrial bioenergetics respect to the energy requirements of pre- and post-synaptic compartments. |
| Databáze: | OpenAIRE |
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