Roberto Federico Villa
University of Pavia, Italy
Posters & Accepted Abstracts: Neurochem Neuropharm
Human neuroimaging studies have shown brain energy metabolism abnormalities in mood disorders, indicating the normalization of tissutal bioenergetics after anti-depressants├ó┬?┬? (ADs) treatment. However, several experimental studies suggest that antidepressants are inhibitors of mitochondrial function, while others indicate positive effects. In this study, the effects of 21-day treatment with the tricyclic antidepressant Desipramine (15 mg/kg, i.p.) were evaluated on energy metabolism of rat frontal cerebral cortex. Because of brain mitochondria micro-heterogeneity, (a) non-synaptic mitochondria in vivo located in neuronal perikaryon and (b) two types of intra-synaptic mitochondria in vivo located in synapses (├ó┬?┬?light├ó┬?┬Ł and ├ó┬?┬?heavy├ó┬?┬Ł) were used. The following enzyme activities have been assayed: citrate synthase (CS), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) for Krebs├ó┬?┬? cycle; NADH-cytochrome c reductase (CCR), cytochrome oxidase (COX) for Electron Transport Chain; glutamate dehydrogenase (GlDH), glutamate-oxaloacetate transaminase (GOT), glutamatepyruvate transaminase (GPT) for glutamate and related amino acids metabolism. In controls, energy-linked enzyme activities are differently expressed in the considered mitochondria, whose metabolic individuality is reflected by enzyme kinetics, as previously shown in physiological aging, experimental physiopathology and after pharmacological treatments. Desipramine modified the catalytic properties of energy-linked enzymes differentially respect to the types of intra-synaptic mitochondria, explaining at subcellular level and on functional proteomic basis the previously observed conflicting results about ADs on mitochondria. In this research, Desipramine exerted on the energy metabolism distinctive effects on post-synaptic compartment and on pre-synaptic terminal: the present data allow to integrate from a bioenergetic point of view the pharmacodynamic features of this paradigmatic drug.